Journal: Circ Arrhythm Electrophysiol

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Abstract

A Randomized Study of CRT-D versus Dual-Chamber ICD in Ischemic Cardiomyopathy with Narrow QRS: The NARROW-CRT Study.

Muto C, Solimene F, Gallo P, Nastasi M, ... Ciardiello C, Tuccillo B
Background: -Current recommendations require a QRS duration of ≥120ms 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 <120ms 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-D and D-ICD arm, respectively). The primary endpoint was the HF clinical composite response, which scores patients as improved, unchanged, or worsened. The secondary endpoint was the cumulative survival from HF hospitalization and HF death. An additional secondary endpoint was the composite of HF hospitalization, HF death and spontaneous ventricular fibrillation. Twenty-three of 56 CRT-D patients showed an improvement in their clinical composite response at 1 year, compared with 9 of 55 D-ICD patients (41% versus 16%, p=0.004). After a median follow-up of 16 months, the CRT-D arm showed a non-significant higher survival from HF hospitalization and HF death (p=0.077), and a significantly higher survival from the combined endpoint of HF hospitalization, HF death and spontaneous ventricular fibrillation (p=0.028). Conclusions: -In this comparison of CRT-D and D-ICD, 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; Identifier: NCT01577446.

Circ Arrhythm Electrophysiol: 16 Apr 2013; epub ahead of print
Muto C, Solimene F, Gallo P, Nastasi M, ... Ciardiello C, Tuccillo B
Circ Arrhythm Electrophysiol: 16 Apr 2013; epub ahead of print | PMID: 23592833
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More Musing About the Interrelationships of Atrial Fibrillation and Atrial Flutter and Their Clinical Implications.

Waldo AL
The interrelationship between atrial fibrillation (AF) and atrial flutter (AFL) has long been recognized both in patients and animal models(1). There are two important aspects of this interrelationship relevant to the paper by Mohanty et al.(2) in this issue of this journal. First is the fact that AF virtually always precedes the onset of classical cavotricuspid isthmus (CTI) dependent AFL, and second, the development of classical CTI AFL requires the development or presence of a line of block in the right atrium between the venae cavae(1). The first aspect probably was initially recognized by Sir Thomas Lewis(3), who, in studies in the normal canine heart, burst paced the right atrium, and obtained mostly transient AF, but sometimes sustained AFL. Lewis "mapped" the AFL, and concluded that AFL was due to reentry around the great veins, i.e., the superior and inferior vena cavae. This conclusion became well accepted. The second aspect was addressed by Rosenbleuth and Garcia-Ramos(4), who postulated that the reason it was so difficult for Lewis et al. to induce AFL was because there was short circuiting of the AFL reentrant circuit by conduction across the atria in the region between the vena cavae (from the left atrium or to the right atrium or vice versa) making the reentrant circuit impossible to sustain. Therefore, in studies in the canine heart (1947), they created conduction block between the vena cavae, either with a crush lesion (permanent block) or by painting cocaine on the atrial epicardium in the intercaval region (transient block), and, with burst atrial pacing, easily induced AFL. The latter occurred consistently in the presence of the crush lesion, but only transiently with the use of cocaine, as the effects of the cocaine wore off.

Circ Arrhythm Electrophysiol: 06 May 2013; epub ahead of print
Waldo AL
Circ Arrhythm Electrophysiol: 06 May 2013; epub ahead of print | PMID: 23650308
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Abstract

Electrophysiologic Features Differentiating the Atypical AV Node-Dependent Long RP Supraventricular Tachycardias.

Ho RT, Frisch DR, Pavri BB, Levi SA, Greenspon AJ
Background: -Diagnosing atypical AVN - dependent long RP SVTs can be challenging. Methods and results: -Nineteen patients with 20 SVTs (atypical AVNRT without (n=11)/ with (n=3) a bystander nodo-fascicular (NF) accessory pathway (AP), orthodromic reciprocating tachycardia (ORT) using a decremental atrio-ventricular (PJRT, n=4) or nodo-fascicular (NFRT, n=2)) AP underwent electrophysiologic study. Post-pacing interval (PPI) - tachycardia cycle length (TCL), corrected PPI (cPPI), ΔVA, ΔHA, ΔAH values and responses to His-refractory VPDs were studied. Compared to AVNRT, ORT patients were younger (42 ± 13yrs vs. 54 ± 19yrs, p=0.036) and female (5/6 (83%) vs. 3/14 (21%), p=0.036); TCLs were similar (435ms vs. 429ms, CI= - 47.5 - 35.5). PPI - TCL was shorter for ORT (118ms vs. 176ms, CI= 26.3 - 89.7) but only 50% had PPI - TCL < 115ms while 5/6 (83%) had PPI - TCL < 125ms (sensitivity: 83%, specificity: 100%). Corrected PPI < 110ms, ΔVA < 85ms, and ΔHA < 0ms had equivalent sensitivity (67%) and 100% specificity for ORT. Compared to PJRT, NFRT/AVNRT had longer ΔAH (29ms vs. 10ms, CI= 3.03 - 35.0) or AH(SVT) < AH(NSR). His-refractory VPDs advanced (4/8 (50%)), delayed (4/8 (50%)), or terminated (5/8 (63%)) SVT in all AP patients. Conclusions: -This unusual SVT requires separate maneuvers to delineate its upper and lower circuit. Standard entrainment criteria are modestly sensitive but highly specific for ORT; and PPI - TCL of 125ms appears better than 115ms. The ΔAH criteria or paradoxically, AH(SVT) < AH(NSR) differentiates NFRT/AVNRT from PJRT. Bystander APs were only identified by His-refractory VPDs.

Circ Arrhythm Electrophysiol: 29 Apr 2013; epub ahead of print
Ho RT, Frisch DR, Pavri BB, Levi SA, Greenspon AJ
Circ Arrhythm Electrophysiol: 29 Apr 2013; epub ahead of print | PMID: 23629734
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Abstract

Cardiac Resynchronization Therapy Improves Altered Na Channel Gating in Canine Model of Dyssynchronous Heart Failure.

Aiba T, Barth AS, Hesketh GG, Hashambhoy YL, ... Kass DA, Tomaselli GF
Background: -Slowed Na(+) current (INa) decay and enhanced late INa (INa-L) prolong the action potential duration (APD) and contribute to early afterdepolarizations (EADs). Cardiac resynchronization therapy (CRT) shortens APD compared to dyssynchronous heart failure (DHF), however, the role of altered Na(+) channel gating in CRT remains unexplored. Methods and results: -Adult dogs underwent left-bundle branch ablation and right atrial pacing (200 bpm) for 6 weeks (DHF) or 3 weeks followed by 3 weeks of biventricular pacing at the same rate (CRT). INa and INa-L were measured in left ventricular myocytes from non-failing (NF), DHF and CRT dogs. DHF shifted voltage dependence of INa availability by -3 mV compared to NF, enhanced intermediate inactivation and slowed recovery from inactivation. CRT reversed the DHF-induced voltage shift of availability, partially reversed enhanced intermediate inactivation but did not affect DHF-induced slowed recovery. DHF markedly increased INa-L compared to NF. CRT dramatically reduced DHF-induced enhanced INa-L, abbreviated the APD and suppressed EADs. CRT was associated with a global reduction in phosphorylated CaMKII, which has distinct effects on inactivation of cardiac Na(+) channels. In a canine AP model, alterations of INa-L are sufficient to reproduce the effects on APD observed in DHF and CRT myocytes. Conclusions: -CRT improves DHF-induced alterations of Na(+) channel function, especially suppression of INa-L, thus abbreviating the APD and reducing the frequency of EADs. Changes in the levels of phosphorylated CaMKII suggest a molecular pathway for regulation of INa by biventricular pacing of the failing heart.

Circ Arrhythm Electrophysiol: 06 May 2013; epub ahead of print
Aiba T, Barth AS, Hesketh GG, Hashambhoy YL, ... Kass DA, Tomaselli GF
Circ Arrhythm Electrophysiol: 06 May 2013; epub ahead of print | PMID: 23650309
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Abstract

Increased Incidence of Esophageal Thermal Lesions using the Second-Generation 28mm Cryoballoon.

Metzner A, Burchard A, Wohlmuth P, Rausch P, ... Kuck KH, Wissner E
Background: -Pulmonary vein isolation (PVI) is an established treatment option for atrial fibrillation (AF). To date, the incidence and quality of ablation-induced esophageal thermal lesions (ETL) using the recently introduced second-generation cryoballoon (CB, ArcticFront Advance, Medtronic) is unknown. Methods and results: -In patients with drug-refractory paroxysmal AF or short-standing persistent AF, PVI was performed using the second-generation CB. The endoluminal esophageal temperature was monitored via a temperature probe. Following PVI, esophagogastroduodenoscopy (EGD) was performed to assess the incidence of ETL. In 50 patients (18 female, age 61±11 years, left atrial diameter 43±5 mm) successful CB-based PVI was performed. Lowest median balloon-temperature and esophageal temperature for the right superior pulmonary vein (PV) was -51°C and 35.8°C, -47°C and 35°C for the right inferior PV, -51°C and 34.4°C for the left superior PV, -48°C and 34.6°C for the left inferior PV and -54°C and 34.5°C for the left common PV, respectively. EGD performed 2±1 days post ablation demonstrated superficial thermal lesions and thermal ulcerations in 1/50 (2%) and 5/50 (10%) patients, respectively. In patients with ETL, during at least 1 freeze cycle the endoluminal esophageal temperature measured less than 3.0°C. All thermal lesions were in the healing process upon repeat EGD 4±2days after initial endoscopy. Conclusions: -Using the second-generation 28mm CB, ETL were detected in 6/50 (12%) patients. All ETL were in the healing process upon repeat EGD. An esophageal temperature safety cut-off may prove valuable in the prevention of ETL and requires further evaluation.

Circ Arrhythm Electrophysiol: 09 Jun 2013; epub ahead of print
Metzner A, Burchard A, Wohlmuth P, Rausch P, ... Kuck KH, Wissner E
Circ Arrhythm Electrophysiol: 09 Jun 2013; epub ahead of print | PMID: 23748208
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Abstract

Mechanical Alternans Is Associated with Mortality in Acute Hospitalized Heart Failure: Prospective Mechanical Alternans Study (MAS).

Kim R, Cingolani O, Wittstein I, McLean R, ... Henrikson CA, Tereshchenko LG
-Acute hospitalized heart failure (AHHF) is associated with 40-50% risk of death or rehospitalization within 6 months post-discharge. Timely (before hospital discharge) risk stratification of AHHF patients is crucial. We hypothesized that mechanical alternans (MA) and T-wave alternans (TWA) is associated with post-discharge outcomes in AHHF patients. . Methods and results: -A prospective cohort study was conducted in the intensive cardiac care unit (ICCU) and enrolled 133 patients (59.6±15.7 y.; 65% men) admitted with AHHF. Surface ECG and peripheral arterial blood pressure waveform via arterial line were recorded continuously during the ICCU stay. MA and TWA were measured by enhanced modified moving average method. All-cause death or heart transplant served as a combined primary endpoint. MA was observed in 28 patients (25%), while TWA was detected in 33 patients (33%). If present, MA was tightly coupled with TWA. Mean TWA amplitude was larger in patients with both TWA and MA, as compared to patients with lone TWA (median 37(IQR 26-61) vs. 22(21-23) μV; P=0.045). After a median of 10 months post-discharge, 42 (38%) patients died and 2 had heart transplants. MA was associated with the primary endpoint in univariable Cox model [HR 1.84(95%CI 1.00-3.40); P=0.05], and after adjustment for left ventricular ejection fraction, NYHA HF class, and implanted ICD/CRT-D device, [HR 2.12 (95%CI 1.13-3.98); P=0.020]. TWA without consideration of simultaneous MA was not significantly associated with primary endpoint (HR 1.42; (95%CI 0.77-2.64); P=0.260).

Circ Arrhythm Electrophysiol: 02 Mar 2014; epub ahead of print
Kim R, Cingolani O, Wittstein I, McLean R, ... Henrikson CA, Tereshchenko LG
Circ Arrhythm Electrophysiol: 02 Mar 2014; epub ahead of print | PMID: 24585716
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Abstract

Inhibition of Late Sodium Current by Mexiletine: A Novel Pharmotherapeutical Approach in Timothy Syndrome.

Gao Y, Xue X, Hu D, Liu W, ... Li C, Yan GX
Background: -Timothy syndrome (TS) is a rare LQTS caused by CACNA1C mutations G406R in exon 8A (TS1) and G402S/G406R in exon 8 (TS2). Management of TS is a challenge and prognosis is poor. This study aimed to explore the inheritance pattern and mechanism of an INa blocker, mexiletine, to improve clinical manifestations in TS. Methods and results: -A 2-year-old Chinese girl with a typical TS1 phenotype underwent candidate gene screening. Qualitative and quantitative cloning sequence and analyses for mosaicism were performed on family members. Therapeutic effects of mexiletine were evaluated using ECG and Holter monitoring. The electrophysiologic effect of mexiletine was evaluated in a TS model using rabbit ventricular wedges. The proband with severe syndactyly and delayed language skills was identified harboring a G406R mutation in CACNA1C. Her baseline-ECG showed markedly prolonged QTc, 2:1 atrioventricular block (AVB) and macro T wave alternans (TWA). G406R was absent in her mother but expressed in her father\'s oral mucosa, sperm and white blood cells, indicating a mosaic carrier. Though asymptomatic he exhibited mild QTc prolongation (470-490 ms) and syndactyly. Mexiletine shortened QTc from 584 to 515 ms, blunted QT-RR relationship, and abolished 2:1 AVB and TWA in the girl. In in vitro studies, mexiletine inhibited late INa with IC50 of 17.6±1.9 μM and attenuated brady-dependent QT prolongation and reduced QT-RR slope in the TS model using BayK 8644. Conclusions: -Mexiletine shortened QTc, attenuated QT-RR slope, abolished 2:1 AV block and TWA in a TS1 patient and TS model via inhibition of late INa.

Circ Arrhythm Electrophysiol: 11 Apr 2013; epub ahead of print
Gao Y, Xue X, Hu D, Liu W, ... Li C, Yan GX
Circ Arrhythm Electrophysiol: 11 Apr 2013; epub ahead of print | PMID: 23580742
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Abstract

Myocardial Infarction and Atrial Fibrillation: Importance of Atrial Ischemia.

Alasady M, Shipp NJ, Brooks AG, Lim HS, ... Abhayaratna W, Sanders P
-Myocardial infarction (MI) is associated with the development of atrial fibrillation (AF). We aimed to characterize the atrial abnormalities due to MI and determine the role of ischemia to the AF substrate. Method and Results-Forty-four sheep were studied. MI was induced by occlusion of the circumflex artery (LCX) or left anterior descending artery (LAD). Excluding 11 with fatal arrhythmias, equal groups of animals (LCX; LAD; and sham operated) underwent sequential electrophysiology study over 45 minutes to determine: atrial effective refractory periods (ERP); conduction velocity (CV); conduction heterogeneity index (CHI); and AF inducibility. Post-mortem evaluation was performed with TTC staining. MI resulted in greater LV dysfunction (P<0.05), LA pressure (p<0.0003) and reduction in atrial ERP (P<0.0001) compared to control. TTC staining demonstrated that the LCX and not the LAD group had atrial infarction. The LCX group demonstrated the following compared to the LAD or control groups: greater slowing in atrial CV (P<0.0001 and P<0.001); increased absolute range of conduction phase delay (P<0.001 and P<0.001); increased CHI (P<0.0001 and P<0.001); greater AF vulnerability (P<0.05 for both); and longer AF duration (p<0.05 for both). LAD group had modest but significant slowing in CV (P<0.01) but no change in CHI or AF duration compared to control.

Circ Arrhythm Electrophysiol: 21 Jul 2013; epub ahead of print
Alasady M, Shipp NJ, Brooks AG, Lim HS, ... Abhayaratna W, Sanders P
Circ Arrhythm Electrophysiol: 21 Jul 2013; epub ahead of print | PMID: 23873140
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Abstract

Outcome of Ventricular Tachycardia Ablation in Patients with Nonischemic Cardiomyopathy: The Impact of Noninducibility.

Piers SR, Leong DP, van Huls van Taxis CF, Tayyebi M, ... Schalij MJ, Zeppenfeld K
Background: -Ablation failure and recurrence rates after ventricular tachycardia (VT) ablation in nonischemic cardiomyopathy (NICM) are high and the optimal procedural endpoint is not well defined. This study assessed the outcome after ablation, the impact of noninducibility and other potential predictors of VT recurrence. Methods and results: -Forty-five patients with NICM (60±16 years, LVEF 44±14%) accepted for VT ablation were included. Epicardial mapping was performed in 29 (64%). A median of 2 (first-to-third quartile, 2-4) VTs (cycle length [CL] 342±77ms) were induced per patient. After ablation, the complete programmed electrical stimulation protocol (3 drive CL, 3 extrastimuli ≥200ms, burst, ≥2 sites) was repeated. Complete success (non-inducibility of any monomorphic VT) was achieved in 17 patients (38%), partial success (elimination of clinical VT, persistent inducibility of non-clinical VT) in 17 patients (38%), and failure (persistent inducibility of clinical VT) in 11 patients (24%). During 25±15 months follow-up VT occurred in 24 patients (53%), but the 6-month VT burden was reduced by ≥75% in 79%. Recurrence rates were low after complete procedural success (18%), but high after both partial success (77%) and failure (73%). Non-complete procedural success was the strongest predictor of VT recurrence (hazard ratio 8.20, 95% confidence interval 2.37-28.43, p=0.001). Conclusions: -Although 53% of patients had VT during follow-up, the 6-month VT burden was decreased by ≥75% in 79%. Recurrence rates are low after complete procedural success, but high after both partial success and failure. Non-complete procedural success was the strongest predictor of VT recurrence.

Circ Arrhythm Electrophysiol: 25 Apr 2013; epub ahead of print
Piers SR, Leong DP, van Huls van Taxis CF, Tayyebi M, ... Schalij MJ, Zeppenfeld K
Circ Arrhythm Electrophysiol: 25 Apr 2013; epub ahead of print | PMID: 23619893
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Abstract

Characterisation of the Left Atrial Neural Network and its Impact on Autonomic Modification Procedures.

Malcolme-Lawes LC, Lim PB, Wright I, Kojodjojo P, ... Peters NS, Kanagaratnam P
Background: -Left atrial (LA) ganglionated plexi (GP) are part of the intrinsic cardiac autonomic nervous system and implicated in the pathogenesis of atrial fibrillation (AF). High frequency stimulation (HFS) is used to identify GP sites in humans. The effect of ablation on neural pathways connecting GPs in humans is unknown. Methods and results: -30 patients undergoing LA ablation with autonomic modification were recruited. In patients with persistent AF, endocardial cont-HFS identified GP sites producing AV block. Following right lower GP (RLGP) ablation (N=5), 2 of 15 sites remained positive whereas following ablation of other GPs (N=5), leaving RLGP intact, all 19 sites remained positive (RLGP vs Other GP p<0.005), indicating that neural pathways between LA GPs and the AV node are via the RLGP. In 20 patients with paroxysmal AF, sync-HFS identified sites initiating PV ectopy. Following PV isolation (N=8) no sites remained positive. Following local GP ablation (N=9) 3 of 14 sites remained positive suggesting neural connections to the PV were disrupted by both PVI and GP ablation. Heart rate variability indices reduced significantly after right upper GP (RUGP) ablation alone, suggesting that neural pathways from the LA to the SA node travel via the RUGP. Conclusions: -We have demonstrated neural pathways connecting LA GPs with the PVs, AV node and SA node. The effects of HFS at GP sites can be prevented by ablating the GP site or the neural pathway. This further delineates the mechanism via which PV isolation prevents AF and highlights important caveats for autonomic modification endpoints.

Circ Arrhythm Electrophysiol: 11 Apr 2013; epub ahead of print
Malcolme-Lawes LC, Lim PB, Wright I, Kojodjojo P, ... Peters NS, Kanagaratnam P
Circ Arrhythm Electrophysiol: 11 Apr 2013; epub ahead of print | PMID: 23580743
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Abstract

Dynamic Analysis of Cardiac Rhythms for Discriminating Atrial Fibrillation from Lethal Ventricular Arrhythmias.

Demazumder D, Lake DE, Cheng A, Moss TJ, ... Tomaselli GF, Moorman JR
Background: -Implantable cardioverter-defibrillators (ICDs), the first-line of therapy for preventing sudden cardiac death in high-risk patients, deliver "appropriate" shocks for termination of ventricular tachycardia/fibrillation (VT/VF). A common shortcoming of ICDs is imperfect rhythm discrimination, resulting in the delivery of "inappropriate" shocks for atrial fibrillation (AF). An underexplored area for rhythm discrimination is the difference in dynamic properties between AF and VT/VF. We hypothesized that the higher entropy of rapid cardiac rhythms preceding ICD shocks distinguishes AF from VT/VF. Methods and results: -In a multicenter, prospective, observational study of patients with primary prevention ICDs, 119 patients received shocks from ICDs with stored, retrievable intracardiac electrograms. Blinded adjudication revealed shocks were delivered for VT/VF (62%), AF (23%), and supraventricular tachycardia (15%). Entropy estimation of only 9 ventricular intervals prior to ICD shocks accurately distinguished AF (ROC curve area 0.98; 95% CI 0.93-1.0) and outperformed contemporary ICD rhythm discrimination algorithms. Conclusions: -This new strategy for AF discrimination based on entropy estimation expands on simpler concepts of variability, performs well at fast heart rates, and has potential for broad clinical application.

Circ Arrhythm Electrophysiol: 19 May 2013; epub ahead of print
Demazumder D, Lake DE, Cheng A, Moss TJ, ... Tomaselli GF, Moorman JR
Circ Arrhythm Electrophysiol: 19 May 2013; epub ahead of print | PMID: 23685539
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Abstract

Mitochondria Oxidative Stress, Connexin43 Remodeling, and Sudden Arrhythmic Death.

Sovari AA, Rutledge CA, Jeong EM, Dolmatova E, ... Duffy HS, Dudley SC
Background: -Previously, we showed a mouse model (ACE8/8) of cardiac renin-angiotensin system (RAS) activation has a high rate of spontaneous ventricular tachycardia (VT) and sudden cardiac death (SCD) secondary to a reduction in connexin43 (Cx43) level. Angiotensin-II activation increases reactive oxygen species (ROS) production, and ACE8/8 mice show increased cardiac ROS. We sought to determine the source of ROS and if ROS played a role in the arrhythmogenesis. Methods and results: -Wild-type and ACE8/8 mice with and without two weeks of treatment with L-NIO (nitric oxide synthase inhibitor), sepiapterin (precursor of tetrahydrobiopterin), MitoTEMPO (mitochondria-targeted antioxidant), TEMPOL (a general antioxidant), apocynin (NADPH oxidase inhibitor), allopurinol (xanthine oxidase inhibitor), and ACE8/8 crossed with P67 dominant negative mice to inhibit the NADPH oxidase were studied. Western blotting, detection of mitochondrial ROS by MitoSOX Red, electron microscopy, immunohistochemistry, fluorescent dye diffusion technique for functional assessment of Cx43, telemetry monitoring, and in-vivo electrophysiology studies were performed. Treatment with MitoTEMPO reduced SCD in ACE8/8 mice (from 74% to 18%, P<0.005), decreased spontaneous ventricular premature beats, decreased VT inducibility (from 90% to 17%, P<0.05), diminished elevated mitochondrial ROS to the control level, prevented structural damage to mitochondria, resulted in 2.6 fold increase in Cx43 level at the gap junctions, and corrected gap junction conduction. None of the other antioxidant therapies prevented VT and SCD in ACE8/8 mice. Conclusions: -Mitochondrial oxidative stress plays a central role in angiotensin II-induced gap junction remodeling and arrhythmia. Mitochondria-targeted antioxidants may be effective antiarrhythmic drugs in cases of RAS activation.

Circ Arrhythm Electrophysiol: 04 Apr 2013; epub ahead of print
Sovari AA, Rutledge CA, Jeong EM, Dolmatova E, ... Duffy HS, Dudley SC
Circ Arrhythm Electrophysiol: 04 Apr 2013; epub ahead of print | PMID: 23559673
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Abstract

Left Cardiac Sympathetic Denervation in Long QT Syndrome: Analysis of Therapeutic Non-Responders.

Bos JM, Bos KM, Johnson JN, Moir C, Ackerman MJ
Background: -Long QT Syndrome (LQTS) is a potentially lethal but highly treatable cardiac channelopathy. Treatment options include pharmacotherapy, device therapy, and/or left cardiac sympathetic denervation (LCSD). Here, we sought to determine the characteristics of LQTS patients who have had ≥ 1 LQTS-related breakthrough cardiac event (BCE) following LCSD. Methods and results: -We performed retrospective chart review for 52 consecutive patients (24 male, mean age at diagnosis 10.0±10 years, mean QTc 528±74 ms) with LQTS who underwent LCSD between 2005 through 2010 (mean age at LCSD 14.1±10 years) and have been followed for 3.6 ± 1.3 years. A BCE was defined as either 1) an appropriate VF-terminating ICD shock or 2) arrhythmogenic syncope, seizures, or aborted cardiac arrest following LCSD. Thirty-three patients (61%) had LCSD as primary prevention because of either high risk assessment or beta blocker intolerance. So far, 12/52 (23%) patients (7 male) have experienced at least one BCE post-LCSD. The clinical phenotype of patients with BCE\'s was significantly more severe than patients without a BCE. No BCEs were seen in patients undergoing LCSD for beta blocker intolerance (0/12 vs. 17/40; p < 0.001). Conclusions: -Although a marked reduction in number of cardiac events is usually seen following LCSD, nearly 50% of high risk LQTS patients have experienced at least one post-LCSD breakthrough. Therefore, LCSD must not be viewed as curative or as an ICD-alternative for high risk patients. Prophylactic LCSD may provide another option to counter a suboptimal quality of life resulting from medication-related side effects.

Circ Arrhythm Electrophysiol: 02 Jun 2013; epub ahead of print
Bos JM, Bos KM, Johnson JN, Moir C, Ackerman MJ
Circ Arrhythm Electrophysiol: 02 Jun 2013; epub ahead of print | PMID: 23728945
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Effects of Obstructive Sleep Apnea and its Treatment on Signal-Averaged P-Wave Duration in Men.

Maeno KI, Kasagi S, Ueda A, Kawana F, ... Narui K, Kasai T
Background: -Prolonged P-wave duration, indicating atrial conduction delay, is a potent precursor of atrial fibrillation (AF). Obstructive sleep apnea (OSA) is a risk factor for AF development. We investigated the association of P-wave duration with OSA and its treatment. Methods and results: -We enrolled 80 consecutive men with normal sinus rhythms who underwent polysomnography, had no history of AF or ischemic heart disease, and no evidence of heart failure. Signal-averaged P-wave duration (SAPWD) was measured in all participants. Multivariable regression analysis showed that age, hypertension, and log-transformed apnea-hypopnea index were significantly and independently correlated with SAPWD. SAPWD was repeatedly measured following 1 month of continuous positive airway pressure (CPAP) therapy in 62 patients with moderate-to-severe OSA. As controls, 18 patients with moderate-to-severe OSA were enrolled. Their SAPWD was also measured at baseline and following 1 month without CPAP therapy. No significant change in SAPWD was found between baseline and after 1 month in the controls. However, SAPWD was significantly shortened after 1 month of CPAP therapy (from 137.5±8.6 to 129.7±8.5 ms, P<0.001), and the SAPWD change was significantly different in patients with CPAP therapy compared with controls (P<0.001). In addition, the SAPWD change in patients with CPAP therapy correlated inversely with nightly CPAP usage (r=-0.52, P<0.001). Conclusions: -OSA severity was significantly associated with prolonged SAPWD. CPAP therapy significantly shortened SAPWD in patients with moderate-to-severe OSA. Thus, OSA may cause atrial conduction disturbances, leading to an increased risk of AF development, which may be modifiable by alleviating OSA with CPAP therapy.

Circ Arrhythm Electrophysiol: 20 Mar 2013; epub ahead of print
Maeno KI, Kasagi S, Ueda A, Kawana F, ... Narui K, Kasai T
Circ Arrhythm Electrophysiol: 20 Mar 2013; epub ahead of print | PMID: 23515262
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Arrhythmia Phenotype during Fetal Life Suggests LQTS Genotype: Risk Stratification of Perinatal Long QT Syndrome.

Cuneo BF, Etheridge SP, Horigome H, Sallee D, ... Ackerman MJ, Benson DW
-Fetal arrhythmias characteristic of long QT syndrome (LQTS) include torsades de pointes (TdP) and/or 2° atrioventricular block (AVB), but sinus bradycardia, defined as fetal heart rate <3% for gestational age, is most common. We hypothesized that prenatal rhythm phenotype might predict LQTS genotype and facilitate improved risk stratification and management. Method and Results-Records of subjects exhibiting LQTS fetal arrhythmias were reviewed. Fetal echocardiograms, neonatal ECG, and genetic testing were evaluated. We studied 43 subjects exhibiting fetal LQTS arrhythmias: TdP ± 2° AVB (Group 1, n=7), isolated 2° AVB (Group 2, n=4) and sinus bradycardia (Group 3, n=32). Mutations in known LQTS genes were found in 95% of subjects tested. SCN5A mutations occurred in 71% of Group 1 while 91% of subjects with KCNQ1 mutations were in Group 3. Small numbers of subjects with KCNH2 mutations (n=4) were scattered in all 3 groups. Age at presentation did not differ among groups, and most subjects (n=42) were live born with gestational ages of 37.5±2.8 wks (mean±SD). However, those with TdP were typically delivered earlier. Prenatal treatment in Group 1 terminated (n=2) or improved (n=4) TdP. The neonatal QTc (mean±SE) of Group 1 (664.7±24.9) was longer than neonatal QTc in both Group 2 (491.2±27.6, p=0.004) and Group 3 (483.1±13.7, p<0.001). Despite medical and pacemaker therapy, postnatal cardiac arrest (n=4) or sudden death (n=1) was common among subjects with fetal/neonatal TdP.

Circ Arrhythm Electrophysiol: 01 Sep 2013; epub ahead of print
Cuneo BF, Etheridge SP, Horigome H, Sallee D, ... Ackerman MJ, Benson DW
Circ Arrhythm Electrophysiol: 01 Sep 2013; epub ahead of print | PMID: 23995044
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Abstract

Infant Ventricular Fibrillation Following ST Segment Changes and QRS Widening: A New Cause of Sudden Infant Death?

Miyake CY, Davis AM, Motonaga KS, Dubin AM, Berul CI, Cecchin F
Background: -Ventricular arrhythmia related sudden cardiac arrest in infants with structurally normal hearts is rare. There have been no previously published reports of infants less than 3 months of age with ventricular fibrillation in which a primary diagnosis could not be defined. Methods and results: -Retrospective chart review of 3 unrelated infants less than 2 months of age from 3 different tertiary care centers within the United States and Australia. All 3 infants survived sudden cardiac arrest secondary to multiple episodes of polymorphic ventricular tachycardia and ventricular fibrillation. Each infant demonstrated unique and transient ECG findings consisting of ST changes and QRS widening prior to arrhythmia onset that have not been previously reported. Amiodarone, sedation, sodium channel blocking agents and/or ventricular pacing were effective in suppressing acute events. Despite thorough investigation including genetic testing, the etiology of the ventricular arrhythmias in each of these infants remains unclear. Conclusions: -This is the first report of idiopathic ventricular fibrillation in young infants preceded by stereotypical transient ECG changes. These findings may represent a new, potentially treatable cause of sudden infant death. Recognition of these prodromal changes may be important in future management and survival of these infants.

Circ Arrhythm Electrophysiol: 09 Jun 2013; epub ahead of print
Miyake CY, Davis AM, Motonaga KS, Dubin AM, Berul CI, Cecchin F
Circ Arrhythm Electrophysiol: 09 Jun 2013; epub ahead of print | PMID: 23748209
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Abstract

Sudden Cardiac Death with Autopsy Findings of Uncertain Significance: Potential for Erroneous Interpretation.

Papadakis M, Raju H, Behr ER, De Noronha SV, ... Sheppard MN, Sharma S
Background: -The sudden death of young individuals is commonly attributed to inherited cardiac disorders and familial evaluation is advocated. The identification of pathognomonic histopathological findings, or the absence of cardiac pathology (Sudden Arrhythmic Death Syndrome; SADS) at post-mortem, directs familial evaluation targeting structural disorders or primary arrhythmogenic syndromes, respectively. In a proportion of autopsies, structural abnormalities of uncertain significance are reported. We explored the hypothesis that such sudden cardiac deaths (SCD) represent SADS. Methods and results: -Families (n=340) of index cases of SCD who underwent post-mortem evaluation were evaluated in specialist cardiogenetics clinics. Families in whom the deceased exhibited structural abnormalities of uncertain significance (n=41) such as ventricular hypertrophy, myocardial fibrosis and minor coronary artery disease were included in the study. Results were compared to 163 families with normal post-mortem (SADS). Relatives underwent comprehensive cardiac evaluation. Twenty-one families (51%) with autopsy findings of uncertain significance received a diagnosis based on the identification of an inherited cardiac condition phenotype in ≥ 1 relatives: 14 Brugada syndrome; 4 long-QT syndrome; 1 catecholaminergic polymorphic ventricular tachycardia; 2 cardiomyopathy. A similar proportion of families (47.2%) received a diagnosis in the SADS cohort (p=0.727). An arrhythmogenic syndrome was the predominant diagnosis in both cohorts (46% versus 45%, p=0.863). Conclusions: -Familial evaluation following SCD with autopsy findings of uncertain significance identified a similar proportion of primary arrhythmogenic syndromes to a contemporary series of SADS. Our study highlights the need for accurate interpretation of autopsy findings to avoid erroneous diagnoses, with potentially devastating implications.

Circ Arrhythm Electrophysiol: 13 May 2013; epub ahead of print
Papadakis M, Raju H, Behr ER, De Noronha SV, ... Sheppard MN, Sharma S
Circ Arrhythm Electrophysiol: 13 May 2013; epub ahead of print | PMID: 23671135
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Abstract

Impact of International Normalized Ratio and Activated Clotting Time on Unfractionated Heparin Dosing During Ablation of Atrial Fibrillation.

Hamam I, Daoud EG, Zhang J, Kalbfleisch SJ, ... Weiss R, Hummel JD
Background: -For ablation of atrial fibrillation (AF), it is unclear how baseline INR affects the dosing of unfractionated heparin (UFH). Methods and results: -A retrospective review of 170 consecutive patients undergoing AF ablation with baseline ACT and INR values was performed. Patients were group according to INR < 2.0 (G <2) (n = 129) and INR ≥ 2.0 (G ≥ 2) (n = 41). Clinical variables, UFH doses and ACT values were recorded. An equation was derived to calculate the first bolus of UFH required to achieve an ACT ≥ 300 seconds, and this was subsequently assessed in 168 patients. For the initial 170 patients, the baseline INR (2.47 ± 0.31 vs 1.53 ± 0.31) and ACT (185 ± 26 vs 153 ± 30 seconds) were significantly greater in G ≥ 2 (p < 0.001). The amount of UFH to achieve the first ACT ≥ 300 seconds was significantly higher for G < 2 vs G ≥ 2 (9701 ± 2390 U vs 8268 ± 2366 U; p = 0.0001). Baseline INR, ACT and weight were predictors of the UFH dosage to achieve an ACT ≥ 300 seconds. An equation derived to achieve an ACT ≥ 300 second after a single bolus of UFH met this endpoint in 160/168 patients (95%). Conclusions: -Baseline INR and ACT in addition to weight are the only predictors of UFH dosage needed to achieve an ACT ≥ 300 seconds. A derived equation predicted the UFH dosage to achieve an ACT ≥ 300 seconds.

Circ Arrhythm Electrophysiol: 19 May 2013; epub ahead of print
Hamam I, Daoud EG, Zhang J, Kalbfleisch SJ, ... Weiss R, Hummel JD
Circ Arrhythm Electrophysiol: 19 May 2013; epub ahead of print | PMID: 23685538
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Abstract

Pattern and Timing of the Coronary Sinus Activation to Guide Rapid Diagnosis of Atrial Tachycardia after Atrial Fibrillation Ablation.

Pascale P, Shah AJ, Roten L, Scherr D, ... Haïssaguerre M, Jaïs P
Background: -Atrial tachycardias (AT) during or after ablation of AF frequently pose a diagnostic challenge. We hypothesized that both the patterns and timing of coronary sinus (CS) activation could facilitate AT mapping. Methods and results: -140 consecutive post-persistent AF ablation patients with sustained AT were investigated by conventional mapping. CS activation pattern was defined as "chevron" or "reverse chevron" when the activations recorded on both the proximal and distal CS dipoles were latest or earliest, respectively. The local activation of mid-CS was timed with reference to Ppeak-Ppeak (P-P) interval in lead V1. A ratio, mid-CS activation time to AT cycle length, was computed. Out of 223 diagnosed ATs, 124 were macroreentrant (56%) and 99 were centrifugal (44%). When CS activation was "chevron"/"reverse chevron" (n = 44, 20%), macroreentries were mostly roof-dependent. With reference to P-P interval, mid-CS activation timing showed specific consistency for peritricuspid and perimitral AT. Proximal to distal CS activation pattern and mid-CS activation at 50-70% of the P-P interval (n = 30, 13%) diagnosed peritricuspid AT with 81% sensitivity and 89% specificity. Distal to proximal CS activation and mid-CS activation at 10-40% of the P-P interval (n = 44, 20%) diagnosed perimitral AT with 88% sensitivity and 75% specificity. Conclusions: -The analysis of the patterns and timing of CS activation provides a rapid stratification of most likely macroreentrant ATs and points towards the likely origin of centrifugal ATs. It can be included in a stepwise diagnostic approach to rapidly select the most critical mapping maneuvers.

Circ Arrhythm Electrophysiol: 29 Apr 2013; epub ahead of print
Pascale P, Shah AJ, Roten L, Scherr D, ... Haïssaguerre M, Jaïs P
Circ Arrhythm Electrophysiol: 29 Apr 2013; epub ahead of print | PMID: 23629735
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Abstract

Risk Stratification in Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy Associated Desmosomal Mutation Carriers.

Bhonsale A, James CA, Tichnell C, Murray B, ... Judge DP, Calkins H
Background: -We investigated the role of phenotypic characteristics in stratifying the risk of sustained ventricular arrhythmias in patients harboring Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy (ARVD/C) associated mutations. Methods and results: -Clinical, electrocardiographic and arrhythmic outcome (composite measure of first occurrence of sustained ventricular tachycardia/resuscitated sudden cardiac death/sudden cardiac death/appropriate implantable cardioverter-defibrillator therapy) data was obtained for 215 patients (104 families; 85% PKP-2). Over a mean follow up of 7 years, eighty-six (40%) patients experienced the arrhythmic outcome). Event free survival was significantly lower among probands (p<0.001) and symptomatic (p<0.001) patients. Integration of electrocardiographic (ECG) repolarization and depolarization abnormalities allowed for differential risk categorization. Event free survival at 5 years for the low risk ECG group (0-1 T inversions or minor depolarization changes) was 97% vs.81% for the intermediate risk ECG group (2 T inversions + minor depolarization changes) vs. 33% for the high risk ECG group (≥3 T inversions ± major or minor depolarization changes)(p <0.001). Incremental arrhythmic risk was seen in patients with increasing premature ventricular complex count on a Holter (p <0.001). Proband status {HR 7.7; 95%CI 2.8-22.5; P<0.001}, ≥ 3 Twave inversions {HR 4.2; 95% CI 1.2-14.5; P=0.035} and male gender {HR 1.8; 95%CI 1.2-2.8; P=0.004} were independent predictors of the first arrhythmic event on multivariable analysis. Conclusions: -Pedigree evaluation, an electrocardiogram and a Holter examination provides for comprehensive arrhythmic risk stratification in patients with ARVD/C associated mutations. We propose an approach to risk stratification based on these variables.

Circ Arrhythm Electrophysiol: 13 May 2013; epub ahead of print
Bhonsale A, James CA, Tichnell C, Murray B, ... Judge DP, Calkins H
Circ Arrhythm Electrophysiol: 13 May 2013; epub ahead of print | PMID: 23671136
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Abstract

Pulmonary Vein Isolation Using a Visually-Guided Laser Balloon Catheter: The First 200-Patient Multicenter Clinical Experience.

Dukkipati SR, Kuck KH, Neuzil P, Woollett I, ... Natale A, Reddy VY
Background: -Because of the technical difficulty with achieving pulmonary vein (PV) isolation in the treatment of patients with paroxysmal atrial fibrillation (PAF), novel catheter designs to facilitate the procedure are in development. A visually-guided laser ablation (VGLA) catheter was designed to allow the operator to directly visualize target tissue for ablation, and then deliver laser energy to perform point-to-point circumferential ablation. Single center studies have demonstrated favorable safety and efficacy. We sought to determine the multicenter feasibility, efficacy, and safety of performing PV isolation using the VGLA catheter. Methods and results: -This study includes the first 200 PAF patients treated with the VGLA catheter (33 operators, 15 centers). After transseptal puncture, the VGLA catheter was used to perform PV isolation. Electrical isolation was assessed using a circular mapping catheter. Using the VGLA catheter, 98.8% (95% CI, 97.8-99.5%) of targeted PVs were isolated using a mean of 1.07 catheters/patient. Fluoroscopy and procedure times were 31±21 (mean±sd) and 200±54 min respectively, and improved with operator experience. There were no instances of stroke, TIA, atrio-esophageal fistulas or significant PV stenosis. There was a 2% incidence of cardiac tamponade and 2.5% incidence of phrenic nerve palsy. At 12 months, the drug-free rate of freedom from atrial arrhythmias after one or two procedure was 60.2% (95% CI, 52.7-67.4%) Conclusions: -In this multicenter experience of the first 200 patients treated with the VGLA catheter, PV isolation can be achieved in virtually all patients using a single VGLA catheter with an efficacy similar to radiofrequency ablation.

Circ Arrhythm Electrophysiol: 04 Apr 2013; epub ahead of print
Dukkipati SR, Kuck KH, Neuzil P, Woollett I, ... Natale A, Reddy VY
Circ Arrhythm Electrophysiol: 04 Apr 2013; epub ahead of print | PMID: 23559674
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Abstract

The Insufficiency of Left Anterior Oblique and the Usefulness of Right Anterior Oblique Projection for Correct Localization of a CT-Verified Right Ventricular Lead into the Midseptum.

Osmancik P, Stros P, Herman D, Curila K, Petr R
Background: -The aim of the study was to verify the correct anchoring location for the tip of the right ventricular lead using cardiac CT and to assess the best fluoroscopic and ECG criteria associated with the correct location of the electrode into the mid-septum. Methods and results: -Patients indicated to pacemaker implantation were prospectively enrolled. The RV lead was implanted into the mid-septum according to standard criteria in left anterior oblique (LAO40) view. The cardiac shadow on the right anterior oblique (RAO30) was divided into 4 quadrants perpendicular to the lateral cardiac silhouette and the position of the lead tip was analyzed. The exact position of the lead tip was assessed using CT. Of fifty-one patients, the RV lead was anchored mid-septum in 21 (41.2%; MS group). In 30 (58.8%, non-MS group) patients, the lead was anchored in the adjacent anterior wall. The angle between the lead and horizontal axis on the LAO was similar in both groups. The non-MS group was associated with shorter distances between the tip and cardiac contours in the RAO30 (96.7% of leads in the non-MS group were in the outer quadrant vs. 9.6% in the MS group, p<0.001). The presence of the lead in the middle or inferior quadrants was independently associated with correct mid-septum placement with positive predictive value of 94.7%. Conclusions: -Despite the optimal shape of the LAO, substantial numbers of leads were not anchored in the mid-septum. Knowing the RAO30 lead position can ensure proper mid-septal placement.

Circ Arrhythm Electrophysiol: 06 Jun 2013; epub ahead of print
Osmancik P, Stros P, Herman D, Curila K, Petr R
Circ Arrhythm Electrophysiol: 06 Jun 2013; epub ahead of print | PMID: 23742805
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Abstract

Clinical Impact of Adenosine Triphosphate Injection on Arrhythmogenic Superior Vena Cava in the Context of Atrial Fibrillation Ablation.

Miyazaki S, Taniguchi H, Komatsu Y, Uchiyama T, ... Hirao K, Iesaka Y
Background: -Superior vena cava (SVC) is an infrequent yet an important source of atrial fibrillation (AF). The clinical impact of adenosine triphosphate (ATP) injection on arrhythmogenic SVC has not been evaluated. Methods and results: -43 patients (59 ± 11 years; 32 males) who underwent ATP test for arrhythmogenic SVC after the electrical isolation at either initial procedure or repeat procedure were included. PV antrum isolation was performed at index procedure in all. SVC was isolated following identifying the arrhythmogenicity at index and repeat AF ablation procedure in 34 (79.1%) and 9 (20.9%) patients, respectively. AF originated from the SVC spontaneously and/or under isoproterenol infusion in 30 (75.0%) patients, and immediately after ATP injection in 10 (25.0%) patients. Tachycardia persistently confined to SVC was recorded following electrical isolation in 13 (30.2%) patients. SVC reconnection was provoked by ATP test in 7/36 (19.4%) patients at acute phase. At median 4.0 [2.25-7.5] months after SVC isolation, reconnection was observed in 12/15 (80.0%) patients at repeat procedure. Among 12 patients with reconnection at baseline, SVC reconnection was provoked by ATP test following re-isolation in 1 (8.3%) patient. Among 3 patients without SVC reconnection at baseline, reconnection was provoked by ATP test at chronic phase in 1 patient. Conclusions: -Dormant conduction between an arrhythmogenic SVC and the right atrium can be exposed by ATP administration both immediately and late after isolation, potentially facilitating detection and ablation for isolation.

Circ Arrhythm Electrophysiol: 19 May 2013; epub ahead of print
Miyazaki S, Taniguchi H, Komatsu Y, Uchiyama T, ... Hirao K, Iesaka Y
Circ Arrhythm Electrophysiol: 19 May 2013; epub ahead of print | PMID: 23685540
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Abstract

Sub-Epicardial Action Potential Characteristics Are a Function of Depth and Activation Sequence in Isolated Rabbit Hearts.

Kelly A, Ghouri IA, Kemi OJ, Bishop M, ... Burton FL, Smith GL
Background: -Electrical excitability in the ventricular wall is influenced by cellular electrophysiology and passive electrical properties of the myocardium. Action potential (AP) rise time, an indicator of myocardial excitability, is influenced by conduction pattern and distance from the epicardial surface. This study examined AP rise times and conduction velocity (CV) as the depolarising wavefront approaches the epicardial surface. Methods and results: -Two-photon excitation of di-4-ANEPPS was used to measure electrical activity at discrete epicardial layers of isolated Langendorff-perfused rabbit hearts to a depth of 500μm. Endo-to-epicardial wavefronts were studied during right atrial (RA) or ventricular endocardial pacing. Similar measurements were made with epi-to-endocardial, transverse, and longitudinal pacing protocols. Results were compared with data from a bi-domain model of 3-dimensional electrical propagation within ventricular myocardium. During RA and endocardial pacing, AP rise time (10-90% of upstroke) decreased by ~50% between 500μm and 50μm from the epicardial surface, while CV increased and AP duration was only slightly shorter (~4%). These differences were not observed with other conduction patterns. The depth-dependent changes in rise time were larger at higher pacing rates. Modelling data qualitatively reproduced the behaviour seen experimentally and demonstrated a parallel reduction in peak INa and electrotonic load as the wavefront approaches the epicardial surface. Conclusions: -Decreased electrotonic load at the epicardial surface results in more rapid AP upstrokes and higher CVs compared to the bulk myocardium. Combined effects of tissue depth and pacing rate on AP rise time reduce conduction safety and myocardial excitability within the ventricular wall.

Circ Arrhythm Electrophysiol: 03 Jun 2013; epub ahead of print
Kelly A, Ghouri IA, Kemi OJ, Bishop M, ... Burton FL, Smith GL
Circ Arrhythm Electrophysiol: 03 Jun 2013; epub ahead of print | PMID: 23733913
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Abstract

Influence of Intra-Cardiac Pressure on Spontaneous Ventricular Arrhythmias in Patients with Systolic Heart Failure: Insights from the REDUCEhf Trial.

Reiter MJ, Stromberg KD, Whitman TA, Adamson PB, Benditt DG, Gold MR
Background: -The implantation of a combination hemodynamic monitor-cardioverter-defibrillator in the REDUCEhf study allowed assessment of the relationship between daily intracardiac pressure and occurrence of ventricular arrhythmic (VT/VF) events. Methods and results: -Median estimated pulmonary artery diastolic pressures (ePAD) were calculated every 24 hours in 378 subjects with New York Heart Association functional class II-III heart failure who had at least 60 days of hemodynamic data. Forty six subjects experienced 140 VT/VF events on 80 unique study days in which daily median ePAD was available. The incidence of days with VT/VF events was significantly higher when the daily median ePAD for a subject was elevated, defined as > 1 SD above that subject\'s average median ePAD for the whole study: (2.8 episode days per patient year compared to 1.7 episode days per patient-year; p = 0.040). However, the incidence of days with VT/VF events was not significantly different on days when ePAD was > 25 mm Hg compared to days when ePAD was < 25 mm Hg. For all 378 subjects the risk of VT/VF increased with average median ePAD calculated over the whole follow-up period (OR: 1.072 for a 1 mm Hg increase, 95% CI: 1.023 - 1.124, p = 0.003). Conclusions: -There is significant positive association between average daily median ePAD and risk for VT/VF. Among patients with VT/VF, elevated intracardiac pressures are associated with higher VT/VF risk only when the definition of increased pressure is subject-specific.

Circ Arrhythm Electrophysiol: 20 Mar 2013; epub ahead of print
Reiter MJ, Stromberg KD, Whitman TA, Adamson PB, Benditt DG, Gold MR
Circ Arrhythm Electrophysiol: 20 Mar 2013; epub ahead of print | PMID: 23515265
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Abstract

Contemporary Outcomes of Supraventricular Tachycardia Ablation in Congenital Heart Disease: A Single-Centre Experience in 116 Patients.

Ueda A, Suman-Horduna I, Mantziari L, Gujic M, ... Babu-Narayan SV, Ernst S
Background: -Remote magnetic navigation (RMN)-guided ablation with three-dimensional (3D)-image integration could provide maximum benefit in patients with complex anatomy. We reviewed supraventricular tachycardia (SVT) ablation in adult congenital heart disease (ACHD) patients to assess the contribution of these technologies. Methods and results: -One-hundred-and-fifty-four SVT ablation procedures (228 SVTs) using a 3D-electroanatomic mapping system (EMS) in 116 ACHD patients (mean age 41, 76 male) were classified into three groups; Group A; manual mapping/ablation (n=60 procedures), Group B; RMN-guided mapping/ablation with normal femoral vein access (49), and Group C; RMN-guided mapping/ablation with difficult access (45). Group A included simple anomalies with less SVTs. Group B comprised predominantly Fontan patients with more SVTs. Group C included more complex defects such as intra-atrial baffle or interrupted inferior venous access, in which retrograde aortic and/or superior venous accesses were used exclusively with more frequent use of image integration (97.8%, p<0.001). Acute success was 91.5%, 83.7% and 82.2%, respectively (p=0.370). In group C, fluoroscopy time was the shortest (median 4.2min, p<0.001) despite the longer procedure duration (median 253min, p<0.001). SVTs free rates were 80.4%, 82.4% and 75.8% (p=0.787) during a mean 20months follow-up period. Conclusions: -The combination of RMN, 3D-image integration and EMS facilitated safe and feasible ablation with very low fluoroscopy exposure even in patients with complex anomalies.

Circ Arrhythm Electrophysiol: 19 May 2013; epub ahead of print
Ueda A, Suman-Horduna I, Mantziari L, Gujic M, ... Babu-Narayan SV, Ernst S
Circ Arrhythm Electrophysiol: 19 May 2013; epub ahead of print | PMID: 23685536
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Abstract

Implantable Cardioverter Defibrillators in Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy: Patient Outcomes, Incidence of Appropriate and Inappropriate Interventions, and Complications.

Schinkel AF
Background: -Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is a cardiomyopathy characterized by ventricular arrhythmias and an abnormal right ventricle. Implantable cardioverter defibrillator (ICD) therapy may prevent sudden cardiac death (SCD) in patients with ARVD/C. Currently, an overview of outcomes, appropriate and inappropriate interventions, and complications of ICD therapy in ARVD/C is lacking. Methods and results: -A literature search was performed to identify studies reporting outcome and complications in patients with ARVD/C who underwent ICD implantation. Of 641 articles screened, 24 studies on 18 cohorts were eligible for inclusion. In case of >1 publications on a cohort, the most recent publication was included in the meta-analysis. There were 610 patients (mean age 40.4 years; 42% women), who had an ICD for primary or secondary prevention of SCD. Risk factors for SCD were presyncope (61%), syncope (31%), previous cardiac arrest (14%), ventricular tachycardia (58%), and ventricular fibrillation (6%). Anti-arrhythmic medication consisted mostly of beta-blockers (38%), amiodarone (14%), or sotalol (30%). During the 3.8-year follow-up, annualized cardiac mortality rate was 0.9%, annualized noncardiac mortality rate was 0.8%, and annualized heart transplant rate was 0.9%. The annualized appropriate and inappropriate ICD intervention rates were respectively 9.5% and 3.7%. ICD related complications consisted of difficult lead placement (18.4%), lead malfunction (9.8%), infection (1.4%), lead displacement (3.3%), and any complication (20.3%). Conclusions: -Cardiac and noncardiac mortality rates following ICD implantation in patients with ARVD/C are low. Appropriate ICD intervention occurred at a rate of 9.5%/year. Inappropriate ICD interventions and complications lead to considerable ICD related morbidity.

Circ Arrhythm Electrophysiol: 14 May 2013; epub ahead of print
Schinkel AF
Circ Arrhythm Electrophysiol: 14 May 2013; epub ahead of print | PMID: 23673907
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Abstract

Progression of Atrial Fibrillation after a Failed Initial Ablation Procedure in Patients with Paroxysmal Atrial Fibrillation: A Randomized Comparison of Drug Therapy vs. Re-Ablation.

Pokushalov E, Romanov A, De Melis M, Artyomenko S, ... Mittal S, Steinberg JS
Background: -The aim of this prospective randomized study was to assess if an early re-ablation was superior to AAD therapy in patients with previous failed PVI. Methods and results: -Patients with paroxysmal AF eligible for AAD therapy or re-ablation after a previous failed initial PVI procedure were eligible for this study and were followed for 3 years to assess rhythm by means of an implanted cardiac monitor. After the blanking period post-ablation, 154 patients had symptomatic AF recurrences and were randomized to AAD (N = 77) or to re-PVI (N = 77). At the end follow-up, 61 (79%) patients in AAD group and 19 (25%) patients in re-ablation group demonstrated AF% progression (p<0.01). The AF% at 36 months was significantly greater in the AAD group compared with patients in the re-ablation group, 18.8 ± 11.4% vs 5.6 ± 9.5%, respectively (p<0.01). In addition, 18 (23%) patients in AAD group and 3 (4%) patients in re-ablation group progressed to persistent AF (p<0.01). Moreover, 45 (58%) of the 77 re-ablation group patients became AF/AT-free on no antiarrhythmic drugs; in contrast, in the AAD group, only 9 (12%) of the 77 patients were AF/AT-free (p<0.01) throughout follow-up. Conclusions: -Redo AF ablation was substantially more effective than AAD in reducing the progression and prevalence of AF after the failure of an initial ablation. Clinical Trial registration Information-www.clinicaltrials.gov; Unique Identifier: NCT01709682.

Circ Arrhythm Electrophysiol: 09 Jun 2013; epub ahead of print
Pokushalov E, Romanov A, De Melis M, Artyomenko S, ... Mittal S, Steinberg JS
Circ Arrhythm Electrophysiol: 09 Jun 2013; epub ahead of print | PMID: 23748210
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Abstract

Use of Dabigatran for Peri-Procedural Anticoagulation in Patients Undergoing Catheter Ablation for Atrial Fibrillation.

Bassiouny M, Saliba W, Rickard J, Shao M, ... Lindsay BD, Wazni O
Background: -Pulmonary vein isolation (PVI) for atrial fibrillation (AF) is associated with a transient increased risk of thromboembolic and hemorrhagic events. We hypothesized that dabigatran can be safely used as an alternative to continuous warfarin for the peri-procedural anticoagulation in PVI. Methods and results: -999 consecutive patients undergoing PVI were included; 376 patients were on dabigatran (150 mg) and 623 were on warfarin with therapeutic INR. Dabigatran was held 1 to 2 doses prior to PVI and restarted at the conclusion of the procedure or as soon as patients were transferred to the nursing floor. Propensity score matching was applied to generate a cohort of 344 patients in each group with balanced baseline data. Total hemorrhagic and thromboembolic complications were similar in both groups, before (3.2% vs 3.9%; p = 0.59), and after (3.2% vs 4.1%; p = 0.53) matching. Major hemorrhage occurred in 1.1% vs 1.6% (p = 0.48) before, and 1.2% vs 1.5% (p = 0.74) after matching in the dabigatran vs warfarin group respectively. A single thromboembolic event occurred in each of the dabigatran and warfarin groups. Despite higher doses of intra-procedural heparin, the mean ACT was significantly lower in patients who held dabigatran for 1 or 2 doses than those on warfarin. Conclusions: -Our study found no evidence to suggest a higher risk of thromboembolic or hemorrhagic complications with use of dabigatran for peri-procedural anticoagulation in patients undergoing PVI compared to uninterrupted warfarin therapy.

Circ Arrhythm Electrophysiol: 03 Apr 2013; epub ahead of print
Bassiouny M, Saliba W, Rickard J, Shao M, ... Lindsay BD, Wazni O
Circ Arrhythm Electrophysiol: 03 Apr 2013; epub ahead of print | PMID: 23553523
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Abstract

Transcranial Measurement of Cerebral Microembolic Signals during Pulmonary Vein Isolation: A Comparison of Two Ablation Techniques.

Nagy-Baló E, Tint D, Clemens M, Beke I, ... Edes I, Csanádi Z
Background: -Pulmonary vein isolation (PVI) has increasingly been used to cure atrial fibrillation, but concerns have recently been raised that subclinical brain damage may occur due to microembolization during these procedures. We compared the occurrence of bubble formation seen on intracardiac echocardiography (ICE) and the microembolic signals (MESs) detected by transcranial Doppler on the use of different ablation techniques and anticoagulation strategies. Methods and results: -This prospective study included 35 procedures in 34 consecutive patients (age: 52, SD: 12.8 years; female:male 9:25). PVI was performed with a cryoballoon and the conventional anticoagulation protocol (ACT>250 s) in 10 procedures (Group 1), with a multipolar duty-cycled radiofrequency pulmonary vein ablation catheter (PVAC) and the conventional anticoagulation protocol in 12 procedures (Group 2), and with a PVAC with an aggressive anticoagulation regime (ACT>320 s) in 13 procedures (Group 3). The mean total numbers of MESs detected during the procedures were 833.7 (SD: 727.4) in Group 1, 3142.6 (SD: 1736.4) in Group 2 and 2204.6 (SD: 1078.1) in Group 3 (p=0.0005). MESs were detected mostly during energy delivery in the PVAC groups, while a relatively even distribution of emboli formation was seen during cryoballoon ablations. A significant correlation was found in all groups between the degree of bubble formation on ICE and the number of MESs (p=0.0000). Conclusions: -Duty-cycled RF ablation is associated with significantly more MESs, even when more aggressive anticoagulation is applied. With both techniques most of these microemboli are gaseous in nature.

Circ Arrhythm Electrophysiol: 11 Apr 2013; epub ahead of print
Nagy-Baló E, Tint D, Clemens M, Beke I, ... Edes I, Csanádi Z
Circ Arrhythm Electrophysiol: 11 Apr 2013; epub ahead of print | PMID: 23580744
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Abstract

Combined Na+/Ca2+ Exchanger and L-Type Calcium Channel Block as a Potential Strategy to Suppress Arrhythmias and Maintain Ventricular Function.

Bourgonje VJ, Vos MA, Ozdemir S, Doisne N, ... Sipido K, Antoons G
Background: -L-type calcium channel (LTCC) and Na(+)/Ca(2+) exchanger (NCX) have been implicated in repolarization-dependent arrhythmias, but also modulate calcium and contractility. While LTCC inhibition is negative inotropic, NCX inhibition has the opposite effect. Combined block may therefore offer an advantage for hemodynamics and antiarrhythmic efficiency, particularly in diseased hearts. In a model of proarrhythmia, the dog with chronic atrioventricular block (CAVB), we investigated if combined inhibition of NCX and LTCC with SEA-0400 is effective against dofetilide-induced Torsade de Pointes arrhythmias (TdP), while maintaining calcium homeostasis and hemodynamics. Methods and results: -Left ventricular pressure (LVP) and ECG were monitored during infusion of SEA-0400 and verapamil in anesthetized dogs. Different doses were tested against dofetilide-induced TdP in CAVB dogs. In ventricular myocytes, effects of SEA-0400 were tested on action potentials (AP), calcium transients, and early afterdepolarizations (EAD). In cardiomyocytes, SEA-0400 (1 μM) blocked 66±3% of outward NCX, 50±2% of inward NCX, and 33±9% of LTCC current. SEA-0400 had no effect on systolic calcium, but slowed relaxation despite AP shortening, and increased diastolic calcium. SEA-0400 stabilized dofetilide-induced lability of repolarization and suppressed EADs. In vivo, SEA-0400 (0.4 and 0.8 mg/kg) had no effect on LVP, and suppressed dofetilide-induced TdPs dose-dependently. Verapamil (0.3 mg/kg) also inhibited TdP, but caused a 15±8% drop of LVP. A lower dose of verapamil without effects on LVP (0.06 mg/kg) was not anti-arrhythmic. Conclusions: -In CAVB dogs, SEA-0400 treatment is effective against TdP. Unlike specific inhibition of LTCC, combined NCX and LTCC inhibition has no negative effects on cardiac hemodynamics.

Circ Arrhythm Electrophysiol: 20 Mar 2013; epub ahead of print
Bourgonje VJ, Vos MA, Ozdemir S, Doisne N, ... Sipido K, Antoons G
Circ Arrhythm Electrophysiol: 20 Mar 2013; epub ahead of print | PMID: 23515266
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Abstract

Electrical Reconnection Following PVI is Contingent on Contact Force during Initial Treatment - Results From the EFFICAS I Study.

Neuzil P, Reddy VY, Kautzner J, Petru J, ... Wissner E, Kuck KH
Background: -Pulmonary vein (PV) isolation is the most prevalent approach for catheter ablation of paroxysmal atrial fibrillation (PAF). Long-term success of the procedure is diminished by arrhythmia recurrences occurring predominantly due to reconnections in previously isolated PVs. The aim of the EFFICAS I multicenter study was to demonstrate the correlation between contact force (CF) parameters during initial procedure and the incidence of isolation gaps (\'gap\') at 3 month follow-up (FU). Method and Results-A radiofrequency ablation catheter with integrated contact force sensor (TactiCath®, Endosense, Geneva, Switzerland) was used to perform PV isolation in 46 patients with PAF. During the ablation procedure, the operator was blinded to CF information. At FU, an interventional diagnostic procedure was performed to assess gap location as correlated to index procedure ablation parameters. At FU, 65% (26/40) of patients showed one or more gaps. Ablations with Minimum Force-Time integral (FTI) < 400 g.s showed increased likelihood for reconnection (p<0.001). Reconnection correlated strongly with Minimum CF (p<0.0001) and Minimum FTI (p=0.0007) at the site of gap. Gap occurrence showed a strong trend with lower average CF and average FTI. CF and FTI are generally higher on the right side, although the left anterior segment presents a unique challenge to achieve stable position with good CF. Conclusions: -Minimum CF and Minimum FTI values are strong predictors of gap formation. Optimal contact force parameter recommendations are a target CF of 20 g and a minimum FTI of 400 g.s for each new lesion.

Circ Arrhythm Electrophysiol: 20 Mar 2013; epub ahead of print
Neuzil P, Reddy VY, Kautzner J, Petru J, ... Wissner E, Kuck KH
Circ Arrhythm Electrophysiol: 20 Mar 2013; epub ahead of print | PMID: 23515263
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Abstract

Primary Prevention of Sudden Cardiac Death in a Nonischemic Dilated Cardiomyopathy Population: Reappraisal of the Role of Programmed Ventricular Stimulation.

Gatzoulis KA, Vouliotis AI, Tsiachris D, Salourou M, ... Kallikazaros I, Stefanadis C
Background: -We considered the role of programmed ventricular stimulation (PVS) in primary prevention of sudden cardiac death (SCD) in an idiopathic dilated cardiomyopathy (IDCM) population. Methods and results: -158 IDCM patients underwent PVS. Ventricular tachycardia/ventricular fibrillation (VT/VF) was triggered in 44 patients (group I, 27.8%) versus 114 patients (group II) where VT/VF was not induced. Sixty-nine IDCM patients underwent ICD implantation: 41/44 in Group I and 28/114 in Group II. The major end-points of the study were overall mortality and appropriate ICD activation. Overall mortality during the 46.9 months of mean follow-up was not significantly different between the two groups. Patients with left ventriculat ejection fraction (LVEF) ≤35% (n=119) demonstrated a higher overall mortality rate compared to the patients with LVEF>35% (n=39) (16.8% vs. 10.3%, log rank p=0.025). Advanced NYHA class (III-IV vs I-II) was the single independent and strongest prognostic factor of overall mortality (HR 11.909, p<0.001, CI: 3.106-45.65), as well as of cardiac mortality (HR 14.787, p=0.001, CI: 2.958-73.922). Among ICD recipients, ICD activation rate was significantly higher in group I compared to group II (30/41 patients-73.2% vs. 5/28 patients-17.9%, log-rank p=0.001), either in the form of antitachycardia pacing (68.3% vs. 17.9%, log-rank p=0.001) or in the shock delivery form (51.2% vs. 17.9%, log-rank p=0.05). Induction of VT/VF during PVS in contrast to LVEF was the single independent prognostic factor for future ICD activation (HR 4.195, p=0.007, CI: 1.467-11.994). Conclusions: -Inducibility of VT/VF was associated with an increased likelihood of subsequent ICD activation and SCD surrogate.

Circ Arrhythm Electrophysiol: 15 Apr 2013; epub ahead of print
Gatzoulis KA, Vouliotis AI, Tsiachris D, Salourou M, ... Kallikazaros I, Stefanadis C
Circ Arrhythm Electrophysiol: 15 Apr 2013; epub ahead of print | PMID: 23588627
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Abstract

Isolated Conduction within the Left His-Purkenje System during Sinus Rhythm and Idiopathic Left Ventricle Tachycardia: Findings from Mapping the Whole Conduction System.

Long DY, Dong JZ, Sang CH, Jiang CX, ... Du X, Ma CS
Background: -Functionally, left His-Purkenje system (HPS) is insulated from the adjacent myocardium, and exhibits isolated conduction during sinus rhythm (SR), but in vivo human study is rare. Meanwhile, whether the isolated conduction also exists during idiopathic left ventricle tachycardia (ILVT) is not clearly defined. Current study aimed to delineate the activation sequence and gross anatomy of left HPS during SR and ILVT. Methods and results: -The study involved 25 consecutive patients with ILVT. During SR, left HPS exhibited antegrade activation sequence, and its surrounding myocardium depolarized after HPS in an apical to base direction. During ILVT, the earliest retrograde PPs were mainly located at the middle portion of left posterior fascicle (LPF) [0.5±0.1(0.46~0.58, CI: 95%) of its full length] with an average of 29.5±6.0 mm (19.8~41.5) away from the His position. LPF was depolarized from the earliest retrograde PPs via two opposite wavefronts with significantly shorter activation time than that during SR (15.1±2.1 VS 30.0±3.2ms P<0.001). The left anterior fascicle was depolarized after LPF with an antegrade activation sequence and comparable activation time to that during SR (21.9±2.9 VS 22.0±4.1ms P=0.932). The depolarization of ventricle septum occurred after HPS in an apical to base direction too. Conclusions: -During SR, isolated conduction within the HPS is demonstrated by documenting the reverse activation sequence with its surrounding myocardium. During ILVT, the earliest retrograde PPs were usually recorded at the middle segment of LPF, and the isolated conduction within the HPS remained.

Circ Arrhythm Electrophysiol: 14 May 2013; epub ahead of print
Long DY, Dong JZ, Sang CH, Jiang CX, ... Du X, Ma CS
Circ Arrhythm Electrophysiol: 14 May 2013; epub ahead of print | PMID: 23673906
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Abstract

Three-dimensional Architecture of Scar and Conducting Channels Based on High Resolution ce-CMR: Insights for Ventricular Tachycardia Ablation.

Fernández-Armenta J, Berruezo A, Andreu D, Camara O, ... Frangi A, Brugada J
Background: -Conducting channels (CCs) are the target for ventricular tachycardia (VT) ablation. CCs could be identified with contrast enhanced-cardiac magnetic resonance (ce-CMR) as border zone (BZ) corridors. A three-dimensional (3D) reconstruction of the ce-CMR could allow visualization of the 3D structure of these BZ channels. Methods and results: -We included 21 patients with healed myocardial infarction and VT. A 3D high-resolution 3T ce-CMR was performed prior to CARTO-guided VT ablation. The left ventricular (LV) wall was segmented and characterized using a pixel signal intensity algorithm at 5 layers (endocardium, 25%, 50%, 75%, epicardium). A 3D color-coded shell map was obtained for each layer to depict the scar core and BZ distribution. The presence/characteristics of BZ channels were registered for each layer. Scar area decreased progressively from endocardium to epicardium (scar area/LV area: 34.0±17.4% at endocardium; 24.1±14.7% at 25%; 16.3±12.1% at 50%; 13.1±10.4 at 75%; 12.1±9.3% at epicardium, P <0.01). Forty-five BZ channels (2.1±1.0 per patient, 23.7±12.0 mm length, mean minimum-width 2.5±1.5 mm) were identified, 85% between the endocardium and 50% shell and 76% present in more than one layer. The ce-CMR-defined BZ channels identified 74% of the critical isthmus of clinical VTs and 50% of all the CCs identified in electroanatomical maps. Conclusions: -Scar area in ischemic patients decreases from the endocardium to the epicardium. BZ channels, more commonly seen in the endocardium, display a 3D structure within the myocardial wall that can be depicted with ce-CMR. The use of ce-CMR derived maps to guide VT ablation warrants further investigation.

Circ Arrhythm Electrophysiol: 19 May 2013; epub ahead of print
Fernández-Armenta J, Berruezo A, Andreu D, Camara O, ... Frangi A, Brugada J
Circ Arrhythm Electrophysiol: 19 May 2013; epub ahead of print | PMID: 23685537
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Abstract

Regular Physical Activity and Risk of Atrial Fibrillation: A Systematic Review and Meta-Analysis.

Ofman P, Khawaja O, Rahilly-Tierney CR, Peralta A, ... Gaziano JM, Djousse L
Background: -While previous studies have suggested that competitive athletes have a higher risk of atrial fibrillation (AF) than the general population, limited and inconsistent data are available on the association between regular physical activity (PA) and the risk of AF. Methods and results: -A systematic, comprehensive literature search using MEDLINE, EMBASE, and COCHRANE until 2011. Extracted data from the eligible studies were meta-analyzed using fixed effects model. Four studies, which included 95,526 subjects, were eligible for meta-analysis. For all of the studies included, the extreme groups (i.e. maximum vs. minimal amount of PA) were used for the current analyses. The total number of participants belonging to the extreme groups was 43,672. The pooled odds ratio (95% confidence interval) for AF among regular exercisers was 1.08 (0.97-1.21). Conclusions: -Our data do not support a statistically significant association between regular PA and increased incidence of AF.

Circ Arrhythm Electrophysiol: 20 Mar 2013; epub ahead of print
Ofman P, Khawaja O, Rahilly-Tierney CR, Peralta A, ... Gaziano JM, Djousse L
Circ Arrhythm Electrophysiol: 20 Mar 2013; epub ahead of print | PMID: 23515264
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Abstract

Successful Non-Surgical Treatment of Esophagopericardial Fistulas Following Atrial Fibrillation Catheter Ablation - A Case Series.

Eitel C, Rolf S, Zachäus M, John S, ... Hindricks G, Halm U
Background: -Esophageal perforations are a rare but devastating complication of atrial fibrillation (AF) catheter ablation. Rapid treatment is crucial to avoid permanent disabilities and death. Surgical treatment is considered the treatment of choice. Alternatively, single case reports describe successful esophageal stenting, but others discourage this approach due to fatal consequences. Methods and results: -We present three patients who developed esophagopericardial fistulas following radiofrequency catheter ablation of AF. Diagnosis and management with pericardial drainage and esophageal stenting, as well as long-term follow-up is described. Esophagopericardial fistulas occurred 26, 9 and 18 days after the ablation procedure. Symptoms leading to admission were recurrence of AF (n=1), elective control endoscopy for thermal lesion (n=1) and pain with swallowing (n=1). Computed tomography revealed esophagopericardial fistulas with pericardial effusion in all patients, while contrast leakage and air in the left atrium could be excluded. Broad spectrum antibiotics were initialized and minimally-invasive pericardial drainage as well as esophageal stenting were performed. Stent dislocation occurred in 2 patients and was resolved by repositioning and clipping of the proximal stent end. After 45, 22, and 28 days respectively fistulas appeared closed and stents were removed. During follow-up no embolic or septic events occurred. However, 2 patients underwent dilation of symptomatic esophageal stenosis in the formerly stented region. Conclusions: -An early minimally-invasive approach consisting of pericardial drainage and esophageal stenting proved effective in treating patients with esophagopericardial fistulas. However, constant interdisciplinary communication and attention is needed to promptly recognize and manage potential evolving complications.

Circ Arrhythm Electrophysiol: 02 Jun 2013; epub ahead of print
Eitel C, Rolf S, Zachäus M, John S, ... Hindricks G, Halm U
Circ Arrhythm Electrophysiol: 02 Jun 2013; epub ahead of print | PMID: 23728944
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Abstract

Non-Pharmacologic Control of Post-Operative Supraventricular Arrhythmias Using AV Nodal Fat Pad Stimulation in a Young Animal Open Heart Surgical Model.

Moak JP, Mercader MA, He D, Trachiotis G, ... Martin GR, Jonas RA
Background: -Supraventricular arrhythmias (junctional ectopic tachycardia (JET) and atrial tachyarrhythmias (AT)) frequently complicate recovery from open heart surgery (OHS) in children and can be difficult to manage. Medical treatment of JET can result in significant morbidity. Our goal was to develop a non-pharmacologic approach using autonomic stimulation of selective fat pad (FP) regions of the heart in a young canine model of OHS to control two common post-operative supraventricular arrhythmias. Methods and results: -Eight mongrel dogs, varying in age from 5-8 months and weighting 22 ± 4 kg, underwent OHS replicating a non-transannular approach to tetralogy of Fallot repair. Neural stimulation of the right inferior FP was used to control the ventricular response to supraventricular arrhythmias. Right inferior FP stimulation decreased baseline AV nodal conduction without altering sinus cycle length. AVN Wenckebach cycle length prolonged from 270 ± 33 to 352 ± 89 msec, p=0.02. Atrial fibrillation occurred in 7 animals, simulating a rapid AT. FP stimulation slowed the ventricular response rate from 166 ± 58 to 63 ± 29 bpm, p< 0.001. Post-operative JET occurred in 7 dogs. FP stimulation slowed the ventricular rate during post-operative JET from 148 ± 31 to 106 ± 32 bpm, p < 0.001, and restored sinus rhythm in 7/7 dogs. Conclusions: -Right inferior FP stimulation had a selective effect on the AVN, and slowed the ventricular rate during post-operative JET and AT in our young canine OHS model. FP stimulation may be a useful new technique for managing children with JET and AT.

Circ Arrhythm Electrophysiol: 20 May 2013; epub ahead of print
Moak JP, Mercader MA, He D, Trachiotis G, ... Martin GR, Jonas RA
Circ Arrhythm Electrophysiol: 20 May 2013; epub ahead of print | PMID: 23690377
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Abstract

Efficacy of Implantable Cardioverter Defibrillators in Young Patients with Catecholaminergic Polymorphic Ventricular Tachycardia: Success Depends on Substrate.

Miyake CY, Webster G, Czosek RJ, Kantoch MJ, ... Avasarala K, Atallah J
Background: -The effectiveness of implantable cardioverter-defibrillator (ICD) therapy for the management of catecholaminergic polymorphic ventricular tachycardia (CPVT) in young patients is not known. ICD discharges are not always effective and inappropriate discharges are common, both resulting in morbidity and mortality. Methods and results: -This is a multicenter, retrospective review of young patients with CPVT and ICDs from 5 centers. ICD discharges were evaluated to determine arrhythmia mechanism, appropriateness, efficacy of therapy, and complications. A total of 24 patients were included. Median (IQR) ages at onset of CPVT symptoms and ICD implant were 10.6 (5.0 - 13.8) years and 13.7 (10.7 - 16.3) years respectively. Fourteen patients received 140 shocks. Ten patients (42%) experienced 75 appropriate shocks and 11 patients (46%) received 65 inappropriate shocks. On actuarial analysis, freedom from appropriate shock at 1 year after ICD implant was 75%. Of appropriate shocks, only 43 (57%) demonstrated successful primary termination. All successful appropriate ICD discharges were for ventricular fibrillation (VF). No episodes of polymorphic ventricular tachycardia or bidirectional VT demonstrated successful primary termination. The adjusted mean (95% CI) cycle length of successful discharges was significantly shorter than unsuccessful discharges (168 (152-184) msec vs. 245 (229-262) msec, adjusted p=0.002). Electrical storm occurred in 29% (4/14) and induction of more malignant ventricular arrhythmias in 36% (5/14). There were no deaths. Conclusions: -ICD efficacy in CPVT depends on arrhythmia mechanism. Episodes of VF were uniformly successfully treated whereas polymorphic and bidirectional VT did not demonstrate successful primary termination. Inappropriate shocks, electrical storm and ICD complications were common.

Circ Arrhythm Electrophysiol: 12 May 2013; epub ahead of print
Miyake CY, Webster G, Czosek RJ, Kantoch MJ, ... Avasarala K, Atallah J
Circ Arrhythm Electrophysiol: 12 May 2013; epub ahead of print | PMID: 23667268
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Abstract

Non-Equilibrium Reactivation of Na+ Current Drives Early Afterdepolarizations in Mouse Ventricle.

Edwards AG, Grandi E, Hake JE, Patel S, ... Bers DM, McCulloch AD
-Early-afterdepolarizations (EADs) are triggers of cardiac arrhythmia driven by L-type Ca(2+) current (ICaL) reactivation or sarcoplasmic reticulum (SR) Ca(2+) release and Na(+)/Ca(2+) exchange. In large mammals the positive action potential (AP) plateau promotes ICaL reactivation, and the current paradigm holds that cardiac EAD dynamics are dominated by interaction between ICaL and the repolarizing K(+) currents. However, EADs are also frequent in the rapidly repolarizing mouse AP, which should not readily permit ICaL reactivation. This suggests that murine EADs exhibit unique dynamics, which are key for interpreting arrhythmia mechanisms in this ubiquitous model organism. We investigated these dynamics in myocytes from arrhythmia-susceptible CaMKIIδC-overexpressing mice (Tg), and via computational simulations.

Circ Arrhythm Electrophysiol: 18 Sep 2014; epub ahead of print
Edwards AG, Grandi E, Hake JE, Patel S, ... Bers DM, McCulloch AD
Circ Arrhythm Electrophysiol: 18 Sep 2014; epub ahead of print | PMID: 25236710
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Abstract

Cellular Mechanism Underlying Hypothermia-Induced VT/VF in the Setting of Early Repolarization and the Protective Effect of Quinidine, Cilostazol and Milrinone.

Gurabi Z, Koncz I, Patocskai B, Nesterenko VV, Antzelevitch C
-Hypothermia has been reported to induce ventricular tachycardia and fibrillation (VT/VF) in patients with early repolarization (ER) pattern. This study examines the cellular mechanisms underlying VT/VF associated with hypothermia in an experimental model of ER syndrome (ERS) and examines the effectiveness of quinidine, cilostazol and milrinone to prevent hypothermia-induced arrhythmias. Method and Results-Transmembrane action potentials (AP) were simultaneously recorded from 2 epicardial and 1 endocardial site of coronary-perfused canine left-ventricular wedge preparations, together with a pseudo-ECG. A combination of NS5806 (3-10 μM) and verapamil (1μM) was used to pharmacologically model the genetic mutations responsible for ERS. Acetylcholine (3μM) was used to simulate increased parasympathetic tone, which is known to promote ER. In control, lowering the temperature of the coronary perfusate to induce mild hypothermia (32°C-34°C) resulted in increased J wave area on the ECG and accentuated epicardial AP notch but no arrhythmic activity. In the setting of ER, hypothermia caused further accentuation of the epicardial AP notch, leading to loss of the AP dome at some sites but not others, thus creating the substrate for development of phase-2-reentry and VT/VF. Addition of the Ito antagonist quinidine (5 μM) or the phosphodiesterase III inhibitors cilostazol (10 μM) or milrinone (5 μM), diminished the ER manifestations and prevented the hypothermia-induced phase 2 reentry and VT/VF.

Circ Arrhythm Electrophysiol: 15 Jan 2014; epub ahead of print
Gurabi Z, Koncz I, Patocskai B, Nesterenko VV, Antzelevitch C
Circ Arrhythm Electrophysiol: 15 Jan 2014; epub ahead of print | PMID: 24429494
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Abstract

Atrial Premature Beats During Decrementally Conducting Antidromic Tachycardia.

Sternick EB, Lokhandwala Y, Timmermanns C, Gerken L, ... Hindricks G, Wellens HJ
Background: -Advancement of ventricular activation by an atrial premature beat (APB) given during His bundle refractoriness, followed by resetting of an antidromic tachycardia (AT) in patients (pts) with decrementally conducting accessory pathway (DAP) is a helpful maneuver to prove pathway existence and participation in the circuit. We aim to assess in a large cohort the role of APB during AT in pts with a DAP. Methods and results: -33 pts with a DAP having 34 AT were included in the study: 29 pts had an atriofascicular pathway, 1 had a long atrioventricular (A-V) DAP and 4 had a short A-V fiber. APBs were delivered initially from the lateral RA, scanning diastole with a 10 ms decrement until AT termination or refractoriness. We observed 4 patterns of response following APB during AT: advancement of activation (29 cases), delay (2), advancement followed by delay (3), and termination (7). Eight pts required an earlier APB in order to advance or delay ventricular activation. These 8 pts had a shorter AT cycle length (median of 273 vs. 315 ms, p= 0,003), and had a shorter resetting zone (median coupling interval of 30 vs. 50 ms, p= 0,01). Conclusions: -APB delivered during AT in pts with a DAP advanced and/or delayed ventricular activation in all pts. In 1/5 of cases the AT was terminated by a single APB. In approximately a quarter of the patients an earlier coupled APB was needed to reset AT. The high RA was an adequate stimulation site in all right-sided DAP.

Circ Arrhythm Electrophysiol: 03 Mar 2013; epub ahead of print
Sternick EB, Lokhandwala Y, Timmermanns C, Gerken L, ... Hindricks G, Wellens HJ
Circ Arrhythm Electrophysiol: 03 Mar 2013; epub ahead of print | PMID: 23457113
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Abstract

Transmural Conduction is the Predominant Mechanism of Breakthrough during Atrial Fibrillation: Evidence from Simultaneous Endo-epicardial High Density Activation Mapping.

Eckstein J, Zeemering S, Linz D, Maesen B, ... Allessie MA, Schotten U
Background: -Endo- epicardial dissociation of electrical activations (EED) resulting in transmural conduction of fibrillation waves (breakthroughs) has been postulated to contribute to the complexity of the substrate of atrial fibrillation (AF). The aim of this study was to elucidate the correlation between EED and incidence of breakthrough, and to test the plausibility of transmural conduction versus ectopic focal discharges as sources of breakthrough. Methods and results: -We analyzed high-resolution simultaneous endo-epicardial in vivo mapping data recorded in left atrial free walls of goats with acute AF, 3 weeks and 6 months of AF (all n=7). Waves were analyzed for number, size and width, and categorized according to their origin outside (peripheral wave) or within the mapping area (breakthrough). Breakthrough-incidence was lowest (2.1±1.0%) in acute AF, higher (11.4±6.1%) after 3 weeks (p<0.01 vs acute AF) and highest (14.2±3.8%) after 6 months AF (p<0.001 vs acute AF) and similar in the epicardium and endocardium. The majority of breakthroughs (86%, n=564) could be explained by transmural conduction while only 13% (n=85) could be explained by ectopic focal discharges. Transmural micro-reentry did not play a role as source of breakthrough. Conclusions: -This is the first study to present simultaneous endo-epicardial in vivo mapping data at sites of breakthrough events. Breakthrough incidence and degree of EED increased with increasing AF substrate complexity. In goat left atrial free walls, the majority of breakthroughs can be explained by transmural conduction while ectopic focal discharges play a limited role as source of breakthrough.

Circ Arrhythm Electrophysiol: 19 Mar 2013; epub ahead of print
Eckstein J, Zeemering S, Linz D, Maesen B, ... Allessie MA, Schotten U
Circ Arrhythm Electrophysiol: 19 Mar 2013; epub ahead of print | PMID: 23512204
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Abstract

A Stepwise Approach to the Management of Post-Infarct Ventricular Tachycardia Using Catheter Ablation as the First Line Treatment: A Single Center Experience.

Pauriah M, Cismaru G, Magnin-Poull I, Andronache M, ... Aliot E, de Chillou C
Background: -The occurrence of ventricular tachycardia (VT) following myocardial infarction (MI) is associated with poorer prognosis. In such patients, implantable cardioverter-defibrillators (ICD) are recommended. Catheter ablation of VT is currently recommended only as an adjunctive therapy. Whether a successful VT ablation alone might be a viable strategy in some of these patients, however, remains unknown. The aim of the present study was to evaluate this strategy. Methods and results: -Between January 2002 and December 2011, 189 patients with cardiomyopathy underwent 259 VT ablations in our centre. 45 patients (mean age 65.2±9.6 years, 91% males) with a history of MI and mean left ventricular ejection fraction of 39.7±9.7% matched the study criteria and were included in this analysis. Acute success was obtained in 40/45 (88.9%). During a follow-up, based on our stepwise algorithm [utilising acute success, repeat electrophysiological study (EPS) and recurrence of VT], 19/45 (42.2%) underwent ICD implantation. During a median follow-up of 4.5 (IQR: 2.1-7.0) years, all-cause mortality occurred in 14/45 (31.1%) of patients. Using multivariate Cox regression analysis, age [hazard ratio (HR)=1.13, 95% confidence interval (CI): 1.03-1.22, p=0.007] was the only independent predictor of mortality while ICD implantation was not [HR=0.54, 95% CI: 0.18-1.64, p=0.28) Conclusions: -Our results suggest that a stepwise approach to the management of VT with ablation as a first line treatment in post-infarct patients presenting with VT might be a reasonable option. Further studies are required to confirm these results.

Circ Arrhythm Electrophysiol: 19 Mar 2013; epub ahead of print
Pauriah M, Cismaru G, Magnin-Poull I, Andronache M, ... Aliot E, de Chillou C
Circ Arrhythm Electrophysiol: 19 Mar 2013; epub ahead of print | PMID: 23512203
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Abstract

Effects of Iatrogenic Myocardial Injury on Coronary Microvascular Function in Patients Undergoing Radiofrequency Catheter Ablation of Atrial Fibrillation.

Lim HE, Choi CU, Na JO, Choi JI, ... Hwang C, Kim YH
Background: -Iatrogenic myocardial injury by radiofrequency catheter ablation (RFCA) releases pro-inflammatory substances from damaged myocardium, and these may contribute to endothelial dysfunction in systemic vascular structure. The aim of this study is to evaluate effect of non-ischemic myocardial damage on coronary microvascular function in patients undergoing atrial fibrillation (AF) ablation. Methods and results: -We included 49 patients who underwent AF ablation (paroxysmal AF[PAF] = 25, persistent AF[PeAF] = 24) and 34 controls. Immediately before and after RFCA, index of microvascular resistance (IMR) was assessed at left anterior descending coronary artery and blood samples were obtained for analyses of nitric oxide (NO), activated leukocyte cell adhesion molecule (ALCAM), and lipoprotein-associated phospholipase (LpPLA2). Transthoracic echocardiography was performed at baseline, one day, one month, and 3 months after RFCA. Compared with baseline, IMR, ALCAM, and LpPLA2 increased and NO decreased after RFCA. In 36 subjects with increasing IMR, E/E\' ratio increased at one day and returned to baseline level at 3 months after RFCA. Changes in ALCAM and LpPLA2 between baseline and after RFCA were independently related to the increase in IMR. In 14 subjects (28.6%), arrhythmia recurred. Using a cutoff value of 9.3 mmHg/s, sensitivity was 56.7% and specificity was 91.2% for IMR change in predicting AF recurrence (P = 0.028). Conclusions: -Myocardial damage by RFCA provoked coronary microvascular dysfunction through systemic pro-inflammatory reaction that may contribute to transient diastolic dysfunction. This phenomenon may represent a mechanism for early recurrence of arrhythmia following RFCA. Clinical Trial registration Information-http://cris.cdc.go.kr; Identifier: KCT0000030.

Circ Arrhythm Electrophysiol: 10 Mar 2013; epub ahead of print
Lim HE, Choi CU, Na JO, Choi JI, ... Hwang C, Kim YH
Circ Arrhythm Electrophysiol: 10 Mar 2013; epub ahead of print | PMID: 23476035
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Abstract

Characterization and Mechanisms of Action of Novel NaV1.5 Channel Mutations Associated With Brugada Syndrome.

Calloe K, Refaat MM, Grubb S, Wojciak J, ... Scheinman MM, Schmitt N
Background- Brugada syndrome is a heterogeneous heart rhythm disorder characterized by an atypical right bundle block pattern with ST-segment elevation and T-wave inversion in the right precordial leads. Loss-of-function mutations in SCN5A encoding the cardiac sodium channel Na(V)1.5 are associated with Brugada syndrome. We found novel mutations in SCN5A in 2 different families diagnosed with Brugada syndrome and investigated how those affected Na(V)1.5 channel function. Methods and results- We performed genetic testing of the probands\' genomic DNA. After site-directed mutagenesis and transfection, whole-cell currents were recorded for Na(V)1.5 wild type and mutants heterologously expressed in Chinese hamster ovary-K1 cells. Proband 1 had two novel Na(V)1.5 mutations: Na(V)1.5-R811H and Na(V)1.5-R620H. The Na(V)1.5-R811H mutation showed a significant loss of function in peak Na(+) current density and alteration of biophysical kinetic parameters (inactivation and recovery from inactivation), whereas Na(V)1.5-R620H had no significant effect on the current. Proband 2 had a novel Na(V)1.5-S1218I mutation. Na(V)1.5-S1218I had complete loss of function, and 1:1 expression of Na(V)1.5-wild type and Na(V)1.5-S1218I mimicking the heterozygous state revealed a 50% reduction in current compared with wild type, suggesting a functional haploinsufficiency in the patient. Conclusions- Na(V)1.5-S1218I and R811H are novel loss-of-function mutations in the SCN5A gene causing Brugada syndrome.

Circ Arrhythm Electrophysiol: 19 Feb 2013; 6:177-84
Calloe K, Refaat MM, Grubb S, Wojciak J, ... Scheinman MM, Schmitt N
Circ Arrhythm Electrophysiol: 19 Feb 2013; 6:177-84 | PMID: 23424222
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Abstract

Left Ventricular Epicardial Electrograms Show Divergent Changes in Action Potential Duration in Responders and Non-Responders to Cardiac Resynchronization Therapy.

Chen Z, Hanson B, Sohal M, Sammut E, ... Rinaldi CA, Taggart P
Background: -A consistent feature of electrophysiological remodelling in heart failure is ventricular action potential duration (APD) prolongation. However, the effect of reverse remodelling on APD during cardiac resynchronization therapy (CRT) has not been determined in these patients. We hypothesised (1) CRT may alter APD and (2) that the effect of CRT on APD may be different in patients who exhibit a good haemodynamic response to CRT compared to those with a poor response. Methods and results: -LV activation recovery intervals (ARI), as a surrogate for action potential duration, were measured from the LV epicardium in thirteen patients at day 0, 6 weeks and 6 months following CRT implant. Responders to CRT were defined as those demonstrating a ≥15% reduction in LV end-systolic volume at 6 months. The responder group had a significant reduction in LVARI (mean: -13ms±12ms; median: -16ms, IQR -2ms to -19ms) during RV pacing at 6 months (p<0.05). Conversely the non-responders showed a significant increase in ARI (mean: +22ms±16; median: 17ms, IQR 8ms to 35ms) (p<0.05). (One patient in each group was on Amiodarone.) Conclusions: -In patients with heart failure left ventricular epicardial APD (ARI) altered during CRT. The effect on APD was opposite in patients showing a good haemodynamic response compared to non-responders. The findings may provide explanation for the persistent high incidence of arrhythmias in some patients with CRT and the additional mortality benefit observed in responders of CRT.

Circ Arrhythm Electrophysiol: 10 Mar 2013; epub ahead of print
Chen Z, Hanson B, Sohal M, Sammut E, ... Rinaldi CA, Taggart P
Circ Arrhythm Electrophysiol: 10 Mar 2013; epub ahead of print | PMID: 23476036
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Abstract

Apamin Sensitive Potassium Current Modulates Action Potential Duration Restitution and Arrhythmogenesis of Failing Rabbit Ventricles.

Hsieh YC, Chang PC, Hsueh CH, Lee YS, ... Lin SF, Chen PS
Background: -Apamin-sensitive K currents (I(KAS)) are upregulated in heart failure (HF). We hypothesize that apamin can flatten action potential duration restitution (APDR) curve and reduce ventricular fibrillation (VF) duration in failing ventricles. Methods and results: -We simultaneously mapped membrane potential and intracellular Ca (Ca(i)) in 7 rabbits hearts with pacing-induced HF and in 7 normal hearts. A dynamic pacing protocol was used to determine APDR at baseline and after apamin (100 nM) infusion. Apamin did not change APD(80) in normal ventricles, but prolonged APD(80) in failing ventricles at either long (≥300 ms) or short (≤170 ms) pacing cycle length (PCL), but not at intermediate PCL. The maximal slope of APDR curve was 2.03 [95% CI, 1.73 to 2.32] in failing ventricles and 1.26 [95% CI, 1.13 to 1.40] in normal ventricles at baseline (p=0.002). After apamin administration, the maximal slope of APDR in failing ventricles decreased to 1.43 [95% CI, 1.01 to 1.84] (p=0.018) whereas no significant changes were observed in normal ventricles. During VF in failing ventricles, the number of phase singularities (baseline vs apamin, 4.0 vs 2.5), dominant frequency (13.0 Hz vs 10.0 Hz), and VF duration (160 s vs 80 s) were all significantly (p<0.05) decreased by apamin. Conclusions: -Apamin prolongs APD at long and short, but not at intermediate PCL in failing ventricles. I(KAS) upregulation may be antiarrhythmic by preserving the repolarization reserve at slow heart rate, but is proarrhythmic by steepening the slope of APDR curve which promotes the generation and maintenance of VF.

Circ Arrhythm Electrophysiol: 18 Feb 2013; epub ahead of print
Hsieh YC, Chang PC, Hsueh CH, Lee YS, ... Lin SF, Chen PS
Circ Arrhythm Electrophysiol: 18 Feb 2013; epub ahead of print | PMID: 23420832
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Abstract

Biodegradation of the Outer Silicone Insulation of Endocardial Leads.

Kolodzinska A, Kutarski A, Kozlowska M, Grabowski M, ... Drela N, Opolski G
Background: -Silicone catheter insulation, larynx prostheses undergo biodegradation. The aim of the study was to verify the conviction that outer silicone lead insulation is biostable, inert and to determine the role of macrophages (M) and Staphylococcus (S.) aureus strains in the silicone lead insulation degradation. Methods and results: -Leads removed from 8 patients due to infective and non-infective indications were analyzed with stereomicroscope and classified according to Banacha abrasion classification, additional analysis using scanning electron microscope (SEM) was performed. The examination revealed excavations of different shape and depth in the abraded areas. Fresh silicone insulated lead was cut into fragments. The fragments were cultured with RAW 264.7 macrophage cell line for 9 weeks. Additional lead fragments were placed with S. aureus strains: ATCC 25923, ATCC 29213, K9328H. Lead fragments were also co-cultured with the bacterial strains and RAW M. In SEM analysis diminution in silicone was observed. All S. aureus strains provoked insulation damage after 9 weeks. The lowest level of degradation of insulation concerned ATCC 25923. Silicone lead fragments in co-cultures presented a further gone level of silicone biodegradation. Conclusions: -S. aureus, macrophages separately, and S. aureus and macrophages co-cultures initiate the biodegradation of silicone insulation. Differences in the level of biodegradation between strains of S.aureus were observed, with the most aggressive reaction towards silicone visible in the co-cultures. In vivo silicone biodegradation is initiated by tearing among surfaces of the lead insulation, macrophages may be the crucial cells for the process that may be aggravated by pathogen colonization.

Circ Arrhythm Electrophysiol: 10 Mar 2013; epub ahead of print
Kolodzinska A, Kutarski A, Kozlowska M, Grabowski M, ... Drela N, Opolski G
Circ Arrhythm Electrophysiol: 10 Mar 2013; epub ahead of print | PMID: 23476031
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Abstract

Regional Myocardial Wall Thinning at Multi-Detector Computed Tomography Correlates to Arrhythmogenic Substrate in Post-Infarction Ventricular Tachycardia: Assessment of Structural and Electrical Substrate.

Komatsu Y, Cochet H, Jadidi A, Sacher F, ... Haïssaguerre M, Jaïs P
Background: -A majority of patients undergoing ablation of ventricular tachycardia (VT) have implanted devices precluding substrate imaging with delayed-enhancement magnetic resonance imaging (MRI). Contrast-enhanced multi-detector computed tomography (MDCT) can depict myocardial wall thickness with submillimetric resolution. We evaluated the relationship between regional myocardial wall thinning (WT) imaged by MDCT and arrhythmogenic substrate in post-infarction VT. Methods and results: -We studied 13 consecutive post-infarction patients undergoing MDCT before ablation. MDCT data was integrated with high-density 3D-electroanatomic maps acquired during sinus rhythm (endocardium: 509±291 points/map, epicardium: 716±323 points/map). Low-voltage areas (<1.5 mV) and local abnormal ventricular activities (LAVA) during sinus rhythm were assessed with regard to the WT. A significant correlation was found between the areas of WT<5mm and endocardial low-voltage (correlation-R=0.82, p=0.001), but no such correlation was found in the epicardium. The WT<5mm area was smaller than the endocardial low-voltage area (54cm2 [Q1-Q3: 46-92] versus 71cm2 [Q1-Q3: 59-124], p=0.001). Among a total of 13,060 electrograms reviewed in the whole study population, 538 LAVA were detected and analyzed. LAVA were located within the WT<5mm (469/538 [87%]) or at its border (100% within 23mm). Very late LAVA (>100ms after QRS complex) were almost exclusively detected within the thinnest area (93% in the WT<3mm). Conclusions: -Regional myocardial WT correlates to low-voltage regions and distribution of LAVA critical for the generation and maintenance of post-infarction VT. The integration of MDCT WT with 3D-electroanatomic maps can help focus mapping and ablation on the culprit regions, even when MRI is precluded by the presence of implanted devices.

Circ Arrhythm Electrophysiol: 10 Mar 2013; epub ahead of print
Komatsu Y, Cochet H, Jadidi A, Sacher F, ... Haïssaguerre M, Jaïs P
Circ Arrhythm Electrophysiol: 10 Mar 2013; epub ahead of print | PMID: 23476043
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Abstract

Non-Invasive Localization of Maximal Frequency Sites of Atrial Fibrillation by Body Surface Potential Mapping.

Guillem MS, Climent AM, Millet J, Arenal A, ... Atienza F, Berenfeld O
Background: -Ablation of high frequency sources in patients with atrial fibrillation (AF) is an effective therapy to restore sinus rhythm. However, this strategy may be ineffective in patients without a significant dominant frequency (DF) gradient. The aim of this paper was to investigate whether sites with high frequency activity in human atrial fibrillation (AF) can be identified noninvasively, which should help intervention planning and therapy. Methods and results: -In 14 patients with a history of AF, 67-lead body surface recordings were simultaneously registered with 15 endocardial electrograms from both atria including the highest DF site, which was pre-determined by atrial-wide real-time frequency electroanatomical mapping. Power spectra of surface leads and the body-surface location of the highest DF site were compared with intracardiac information. Highest DFs found on specific sites of the torso showed a significant correlation with DFs found in the nearest atrium (ρ=0.96 for right atrium and ρ=0.92 for left atrium) and the DF gradient between them (ρ=0.93). The spatial distribution of power on the surface showed an inverse relationship between the frequencies vs. the power spread area, consistent with localized fast sources as the AF mechanism with fibrillatory conduction elsewhere. Conclusions: -Spectral analysis of body surface recordings during AF allows a noninvasive characterization of the global distribution of the atrial DFs and the identification of the atrium with the highest frequency, opening the possibility for improved noninvasive personalized diagnosis and treatment.

Circ Arrhythm Electrophysiol: 26 Feb 2013; epub ahead of print
Guillem MS, Climent AM, Millet J, Arenal A, ... Atienza F, Berenfeld O
Circ Arrhythm Electrophysiol: 26 Feb 2013; epub ahead of print | PMID: 23443619
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Abstract

Insights into Atrioventricular Nodal Function from Patients Displaying Dual Conduction Properties: Interactive and Orthogonal Pathways.

Mendenhall GS, Voigt A, Saba S
Background: -There is significant variability observed in the conduction properties of the atrioventricular node. In a subset of hearts impulse transmission tends to fall into two distinct conduction regions, termed the slow and fast pathway, and a further subset are capable of dual conduction of a single input stimulus, termed double firing. Methods and results: -In this manuscript we closely characterize two distinct responses in patients with double firing properties of the atrioventricular node, separating these into discrete types: those with slow and fast pathway interaction and interdependence (interactive), and those with independent pathway properties (orthogonal). We use novel mathematical techniques to evaluate the relative decrement and unique properties of conduction during the overlapping slow and fast pathway conduction zones. Conclusions: -Our analysis demonstrates two distinct patterns of pathway conduction in double firing patients, termed interactive and orthogonal. We show parallel overlapping segments of slow and fast pathway decremental conduction curves in interactive pathways, with no such findings with orthogonal conduction. These findings suggest anatomic correlates of pathway conduction, with interactive pathways likely having a common distal segment, and orthogonal pathways able to independently activate downstream structures.

Circ Arrhythm Electrophysiol: 10 Mar 2013; epub ahead of print
Mendenhall GS, Voigt A, Saba S
Circ Arrhythm Electrophysiol: 10 Mar 2013; epub ahead of print | PMID: 23476032
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Abstract

The Optimal Range of International Normalized Ratio for Radiofrequency Catheter Ablation of Atrial Fibrillation during Therapeutic Anticoagulation with Warfarin.

Kim JS, Jongnarangsin K, Latchamsetty R, Chugh A, ... Morady F, Oral H
Background: -Uninterrupted anticoagulation with warfarin during radiofrequency catheter ablation (RFA) of atrial fibrillation (AF) is associated with a lower risk of periprocedural complications than when warfarin is temporarily discontinued. However, the optimal international normalized ratio (INR) levels during RFA have not been defined. Methods and results: -In this retrospective analysis, RFA was performed in 1133 consecutive patients (mean age: 61±10 years) with paroxysmal (550) or persistent AF (583). Patients were grouped based on the INR on the day of RFA. There was a quadratic relationship between the INR and bleeding and vascular complications (P<0.001). Complications were less prevalent when INR was ≥2.0 and ≤3.0 (5% [31/572]), than when INR was <2.0 (10% [49/485], P=0.004) and >3.0 (12% [9/76], P=0.03). The prevalence of pericardial tamponade (1%) was similar at all INRs. From the quadratic model, the optimal range of INR was calculated as 2.1 to 2.5. INRs <2.0 and >3.0 were associated with a >2-fold increase in complications, with a further steep rise beyond an INR >3.5. Concomitant clopidogrel use was associated with a significant increase in complications at all INRs (OR=3.1, ±95% CI: 1.4-7.4). Unfractionated heparin requirements to maintain a therapeutic ACT during RFA was reduced by 50% in patients with an INR >2.0. Conclusions: -The optimal INR range during uninterrupted periprocedural anticoagulation using warfarin is narrow. Therefore INR levels should be carefully monitored in preparation for radiofrequency catheter ablation of AF.

Circ Arrhythm Electrophysiol: 26 Feb 2013; epub ahead of print
Kim JS, Jongnarangsin K, Latchamsetty R, Chugh A, ... Morady F, Oral H
Circ Arrhythm Electrophysiol: 26 Feb 2013; epub ahead of print | PMID: 23443620
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Abstract

MOG1 Rescues Defective Trafficking of Nav1.5 Mutations in Brugada Syndrome and Sick Sinus Syndrome.

Chakrabarti S, Wu X, Yang Z, Wu L, ... Wang QK, Chen Q
Background: -Loss-of-function mutations in Na(v)1.5 cause sodium channelopathies, including Brugada syndrome (BrS), dilated cardiomyopathy (DCM), and sick sinus syndrome (SSS), however, no effective therapy exists. MOG1 increases plasma membrane (PM) expression of Na(v)1.5 and sodium current (I(Na)) density, thus we hypothesize that MOG1 can serve as a therapeutic target for sodium channelopathies. Methods and results: -Knockdown of MOG1 expression using siRNAs reduced Na(v)1.5 PM expression, decreased I(Na) densities by 2-fold in HEK/Na(v)1.5 cells and nearly abolished I(Na) in mouse cardiomyocytes. MOG1 did not affect Na(v)1.5 PM turnover. MOG1 siRNAs caused retention of Na(v)1.5 in endoplasmic reticulum, disrupted the distribution of Na(v)1.5 into caveolin3-enriched microdomains, and led to redistribution of Na(v)1.5 to non-caveolin-rich domains. MOG1 fully rescued the reduced PM expression and I(Na) densities by Na(v)1.5 trafficking defective mutation D1275N associated with SSS/DCM/atrial arrhythmias. For BrS mutation G1743R, MOG1 restored the impaired PM expression of the mutant protein, and restored I(Na) in a heterozygous state (mixture of wild-type and mutant Na(v)1.5) to a full level of a homozygous wild-type state. Conclusions: -Use of MOG1 to enhance Na(v)1.5 trafficking to PM may be a potential personalized therapeutic approach for some patients with BrS, DCM and SSS in the future.

Circ Arrhythm Electrophysiol: 18 Feb 2013; epub ahead of print
Chakrabarti S, Wu X, Yang Z, Wu L, ... Wang QK, Chen Q
Circ Arrhythm Electrophysiol: 18 Feb 2013; epub ahead of print | PMID: 23420830
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Abstract

Pulmonary Antrum Radial-Linear Ablation for Paroxysmal Atrial Fibrillation: Interim Analysis of a Multicenter Trial.

Zhao X, Zhang J, Hu J, Liao D, ... He B, Liu Z
Background: -Substrate abnormality in pulmonary vein (PV) antrum plays a critical role in mechanism of atrial fibrillation (AF). The present study compares the strategy of PV antrum radial-linear (PAR) ablation to encircling PV isolation for paroxysmal AF. Methods and results: -A total of 86 patients with paroxysmal AF were randomly assigned to PAR ablation group or PV isolation group. The average procedure time was 161±21 min in PAR ablation group and 199±39 min in PV isolation group (P<0.01). The average fluoroscopy time was 25±5 min in PAR ablation group and 32±9 min in PV isolation group (P<0.001). At 14 (15-12) months of follow-up after single procedure, 31 of 42 (74%) patients in PAR ablation group and 22 of 44 patients (50%) in PV isolation group had no recurrence of AF off antiarrhythmic drug (AAD) (P=0.0249); and 36 of 42 patients (86%) in PAR ablation group and 26 of 44 patients (59%) in PV isolation group had no recurrence of AF with AAD (P=0.006). In addition, PAR ablation resulted in greater reduction of LA diameter than encircling PV isolation. Multivariable Cox regression analysis showed that only ablation strategy was independently associated with AF recurrence (HR, 0.31; 95% CI: 0.12-0.78; P=0.013). No major adverse event related to the procedures occurred. Conclusions: -This study suggests that PAR ablation is a potentially effective strategy for treatment of paroxysmal AF warranting further investigation. Clinical Trial registration Information-www.chictr.org; Identifier: ChiCTR-TRC-11001191.

Circ Arrhythm Electrophysiol: 24 Feb 2013; epub ahead of print
Zhao X, Zhang J, Hu J, Liao D, ... He B, Liu Z
Circ Arrhythm Electrophysiol: 24 Feb 2013; epub ahead of print | PMID: 23434517
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Abstract

Association Between Left Ventricular Ejection Fraction Post-Cardiac Resynchronization treatment and Subsequent ICD Therapy for Sustained Ventricular Tachyarrhythmias.

Manfredi JA, Al-Khatib SM, Shaw LK, Thomas L, ... Golden K, Prystowsky EN
Background: -While cardiac resynchronization therapy (CRT) can improve the left ventricular ejection fraction (LVEF), it is not known whether a specific level of improvement will predict future implantable cardioverter defibrillator (ICD) therapy. Methods and results: -CRT-defibrillator (CRT-D) was implanted in 423 patients at one institution between 10/02/2001 through 1/19/2007. A retrospective analysis was performed to evaluate the relationship between post-CRT-D LVEF and ICD therapy for ventricular tachyarrhythmias. A landmark population of 270 patients, with post-CRT-D LVEF measured and no ICD therapy within 1 year of device implantation, was followed for subsequent outcomes. Of these, 22 (8.2%) had subsequent appropriate ICD therapy over a median follow-up of 1.5 years. The estimated 2 year risk of appropriate ICD therapy is 3.0% (95% CI 0-6.3%), 2.1% (95% CI 0-5.0%) and 1.5% (95% CI 0-3.9%) for post-CRT-D LVEF of 45%, 50% and 55%, respectively. In patients with a primary prevention indication for CRT-D, the estimated 2 year risk is 3.3% (95% CI 0-7.3%), 2.5% (95% CI 0-6.1%), and 1.9% (95% CI 0-5.1%) for post-CRT-D LVEF of 45%, 50% and 55%, respectively. Conclusions: -When a CRT responder demonstrates near normalization in LVEF to 45% or more, the incidence of ICD therapy for ventricular arrhythmias becomes low. Future studies are needed to determine whether an ICD is still needed in some of these patients at the time of generator replacement.

Circ Arrhythm Electrophysiol: 26 Feb 2013; epub ahead of print
Manfredi JA, Al-Khatib SM, Shaw LK, Thomas L, ... Golden K, Prystowsky EN
Circ Arrhythm Electrophysiol: 26 Feb 2013; epub ahead of print | PMID: 23443618
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Abstract

Role of Leptin Signaling in the Pathogenesis of Angiotensin II - Mediated Atrial Fibrosis and Fibrillation.

Fukui A, Takahashi N, Nakada C, Masaki T, ... Hara M, Saikawa T
Background: -We examined the hypothesis that leptin signaling contributes to the atrial fibrosis and atrial fibrillation (AF) evoked by angiotensin II (AngII). Methods and results: -Eight-week-old male CL57/B6 (CNT) and leptin-deficient ob/ob mice (Ob) were subcutaneously infused with AngII (2.0 mg/kg/day). Two weeks later, transesophageal burst pacing and an electrophysiological study using isolated perfused hearts were performed. Left atrial tissues were collected to determine interstitial fibrosis by Masson trichrome staining and the expressions of mRNAs related to inflammatory profibrotic signals were assessed. Left atrial fibroblasts were isolated from adult Sprague-Dawley (SD) and Zucker rats. The effects of leptin (100 ng/ml) or AngII (100 nM) treatment were evaluated. In CNT-AngII mice, leptin expression in the left atrium was upregulated (p<0.01). Transesophageal burst pacing induced AF in 88% (7/8) of CNT-AngII mice, but not in Ob-AngII mice (0/8, p<0.01). In isolated perfused hearts, AF was induced only in CNT-AngII mice (4/6, 67%). Inter-atrial conduction time was prolonged in CNT-AngII mice (p<0.01), but not in Ob-AngII mice. The upregulation of collagen 1, collagen 3, TGF-ß1, α-SMA, MCP-1, F4/80 and RANTES mRNA that was seen in CNT-AngII mice, was attenuated in Ob-AngII mice. In cultured SD rat atrial fibroblasts, AngII treatment increased leptin expression (p<0.01). Addition of leptin increased TGF-ß1, α-SMA, MCP-1 and RANTES expressions in SD rat atrial fibroblasts but not in Zucker rat atrial fibroblasts. Conclusions: -Our results demonstrate for the first time that leptin signaling is essential for the development of atrial fibrosis and AF evoked by AngII.

Circ Arrhythm Electrophysiol: 13 Feb 2013; epub ahead of print
Fukui A, Takahashi N, Nakada C, Masaki T, ... Hara M, Saikawa T
Circ Arrhythm Electrophysiol: 13 Feb 2013; epub ahead of print | PMID: 23406575
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Abstract

Engraftment Patterns of Human Adult Mesenchymal Stem Cells Expose Electrotonic and Paracrine Pro-Arrhythmic Mechanisms in Myocardial Cell Cultures.

Askar SF, Ramkisoensing AA, Atsma DE, Schalij MJ, de Vries AA, Pijnappels DA
Background: -After intramyocardial injection, mesenchymal stem cells (MSCs) may engraft and influence host myocardium. However, engraftment rate and pattern of distribution are difficult to control in vivo, hampering assessment of potential adverse effects. In this study, the role of MSCs engraftment patterns on arrhythmicity in controllable in vitro models is investigated. Methods and results: -Co-cultures of 4×10(5) neonatal rat cardiomyocytes (nrCMCs) and 7% or 28% adult human (h) MSCs in diffuse or clustered distribution patterns were prepared. Electrophysiological effects were studied by optical mapping and patch-clamping. In diffuse co-cultures, hMSCs dose-dependently decreased nrCMC excitability, slowed conduction and prolonged APD(90). Triggered activity (14% vs. 0% in controls) and increased inducibility of reentry (53% vs. 6% in controls) were observed in 28% hMSC co-cultures. MSC clusters increased APD(90), slowed conduction locally, and increased reentry inducibility (23%), without increasing triggered activity. Pharmacological heterocellular electrical uncoupling increased excitability and conduction velocity to 133% in 28% hMSC co-cultures, but did not alter APD(90). Transwell experiments showed that hMSCs dose-dependently increased APD(90), APD dispersion, inducibility of reentry and affected specific ion channel protein levels, while excitability was unaltered. Incubation with hMSC-derived exosomes did not increase APD in nrCMC cultures. Conclusions: -Adult hMSCs affect arrhythmicity of nrCMC cultures by heterocellular coupling leading to depolarization-induced conduction slowing and by direct release of paracrine factors that negatively affect repolarization rate. The extent of these detrimental effects depends on the number and distribution pattern of hMSCs. These results suggest that caution should be urged against potential adverse effects of myocardial hMSC engraftment.

Circ Arrhythm Electrophysiol: 18 Feb 2013; epub ahead of print
Askar SF, Ramkisoensing AA, Atsma DE, Schalij MJ, de Vries AA, Pijnappels DA
Circ Arrhythm Electrophysiol: 18 Feb 2013; epub ahead of print | PMID: 23420831
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Abstract

Alternative Research Funding to Improve Clinical Outcomes: The Model of Prediction and Prevention of Sudden Cardiac Death.

Myerburg RJ, Ullmann SG
Although identification and management of cardiovascular risk markers have provided important population risk insights and public health benefits, individual risk prediction remains challenging. Using sudden cardiac death (SCD) risk as a base case, the complex epidemiology of SCD risk and the substantial new funding required to study individual risk are explored. Complex epidemiology derives from the multiple subgroups having different denominators and risk profiles, while funding limitations emerge from saturation of conventional sources of research funding without foreseeable opportunities for increases. A resolution to this problem would have to emerge from new sources of funding targeted to individual risk prediction. In this analysis, we explore the possibility of a research funding strategy that would offer business incentives to the insurance industries, while providing support for unresolved research goals. The model is developed for the case of SCD risk, but the concept is applicable to other areas of the medical enterprise.

Circ Arrhythm Electrophysiol: 10 Feb 2015; epub ahead of print
Myerburg RJ, Ullmann SG
Circ Arrhythm Electrophysiol: 10 Feb 2015; epub ahead of print | PMID: 25669654
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Abstract

Relationship of Sudden Cardiac Death to New-Onset Atrial Fibrillation in Hypertensive Patients with Left Ventricular Hypertrophy.

Okin PM, Bang CN, Wachtell K, Hille DA, ... Dahlöf B, Devereux RB
Background: -Prevalent atrial fibrillation (AF) is associated a higher sudden cardiac death (SCD) rate in some populations and incident AF predicts increased mortality risk in the general population and after myocardial infarction. However, the relationship of SCD to new-onset AF is unclear. Methods and results: -The relationship of SCD to new-onset AF was evaluated in 8,831 hypertensive patients with electrocardiographic (ECG) left ventricular hypertrophy (LVH) with no history of AF, in sinus rhythm on their baseline ECG, randomly assigned to losartan- or atenolol-based treatment. During 4.7∀1.1 years mean follow-up, new-onset AF occurred in 701 patients (7.9%) and SCD in 151 patients (1.7%). In univariate Cox analyses, new-onset AF was associated with a >4-fold higher risk of SCD (HR 4.69, 95% CI 2.96-7.45, p<0.001). In multivariate Cox analyses adjusting for age, sex, race, diabetes, history of heart failure, myocardial infarction, ischemic heart disease, stroke, smoking, serum HDL cholesterol, creatinine, glucose and urine albumin/creatinine ratio as standard risk factors, and for incident myocardial infarction, in-treatment use of digoxin, systolic and diastolic pressure, heart rate, QRS duration, Cornell voltage-duration product and Sokolow-Lyon voltage LVH treated as time-varying covariates, new-onset AF remained associated with a >3-fold increased risk of SCD (HR 3.13, 95% CI 1.87-5.24, p<0.001). Conclusions: -Development of new-onset AF identifies hypertensive patients at increased risk of SCD. Clinical Trials Registration Information-clinicaltrials.gov; Identifier: NCT00338260.

Circ Arrhythm Electrophysiol: 12 Feb 2013; epub ahead of print
Okin PM, Bang CN, Wachtell K, Hille DA, ... Dahlöf B, Devereux RB
Circ Arrhythm Electrophysiol: 12 Feb 2013; epub ahead of print | PMID: 23403268
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Abstract

MRI-Guided Ventricular Tachycardia Ablation: Integration of Late Gadolinium Enhanced 3D Scar in Patients with ICD.

Dickfeld T, Tian J, Ahmad G, Jimenez A, ... Shorofsky S, Jeudy J
Background: -Substrate-guided ablation of ventricular tachycardia (VT) in patients with implanted defibrillators (ICD) relies on voltage mapping to define the scar/border zone. An integrated three-dimensional (3D) scar reconstruction from late gadolinium-enhanced (LGE) MRI could facilitate VT ablations. Methods and results: -Twenty-two patients with ICD underwent contrast-enhanced cardiac MRI (CE-CMR) with a specific absorption rate <2.0W/kg prior to VT ablation. Device interrogation demonstrated unchanged ICD parameters immediately before, after or at 68±21 days follow-up (p>0.05). ICD imaging artifacts were most prominent in the anterior wall and allowed full and partial assessment of LGE in 9±4 and 12±3 of 17 segments, respectively. In fourteen patients with LGE a 3D scar model was reconstructed and successfully registered with the clinical mapping system (accuracy: 3.9±1.8mm). Using ROC-curves bipolar and unipolar voltages of 1.49mV and 4.46mV correlated best with endocardial MRI scar. Scar visualization allowed the elimination of falsely-low voltage recordings (suboptimal catheter contact) in 4.1±1.9% of <1.5mV mapping points. Display of scar border zone allowed identification of excellent pacemapping sites with only limited voltage mapping in 64% of patients. Viable endocardium of >2mm resulted in >1.5mV voltage recordings despite up to 63% transmural midmyocardial scar successfully ablated with MRI guidance. All successful ablation sites demonstrated LGE (transmurality: 68±26%) and were located within 10mm of transition zones to 0-25% scar in 71%. Conclusions: -CE-CMR can be safely performed in selected ICD patients and allows the integration of detailed 3D scar maps into clinical mapping systems. This provides supplementary anatomic guidance to facilitate substrate-guided VT ablations.

Circ Arrhythm Electrophysiol: 28 Jan 2011; epub ahead of print
Dickfeld T, Tian J, Ahmad G, Jimenez A, ... Shorofsky S, Jeudy J
Circ Arrhythm Electrophysiol: 28 Jan 2011; epub ahead of print | PMID: 21270103
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Abstract

Epicardial Ablation for Ventricular Tachycardia: An European Multicenter Study.

Della Bella P, Brugada J, Zeppenfeld K, Merino J, ... Berruezo A, Wijnmaalen AP
Background: -Purpose of this study was to describe the epicardial percutaneous ablation experience of 6 European high volume Ventricular Tachycardia (VT) ablation centers. Methods and results: -Data of 218 patients with Coronary Artery Disease (85, 39.0%), Idiopathic Dilated Cardiomyopathy (67, 30.7%), Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy (13, 6%), Hypertrophic Cardiomyopathy (5, 2.3%) and absence of structural heart disease (48, 22%), undergoing Epicardial subxyphoid access for VT Ablation were collected. The epicardial approach was attempted as first line treatment in 78 patients (35.8%). Acute prevention of VT inducibility was obtained in 156 patients (71.6%). There were no procedure-related deaths. Cardiac tamponade occurred in 8 pts, and abdominal haemorrhage in 1 patient. Six patients died due to electrical storm recurrence within 48 hours from the procedure. After a mean follow up of 17.3 ± 18.2 months, 60 patients (31.4%) presented VT recurrence (39.3% of IDCM pts, 34.7% of CAD patients, 30.8% of ARVD patients, 25% of HCM patients and 17.1% of patients with idiopathic VT. Twenty patients (10.4%) died during follow up: 12 pts due to heart failure, 2 to cardiac arrest, 6 to extra-cardiac causes. Conclusions: -In experienced centers epicardial ablation of ventricular tachycardia has an acceptable risk and favourable outcome. In selected patients, it is reasonable to consider as a first line ablation approach.

Circ Arrhythm Electrophysiol: 15 Aug 2011; epub ahead of print
Della Bella P, Brugada J, Zeppenfeld K, Merino J, ... Berruezo A, Wijnmaalen AP
Circ Arrhythm Electrophysiol: 15 Aug 2011; epub ahead of print | PMID: 21841191
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Abstract

Intraventricular Conduction Delay in a Standard 12-Lead Electrocardiogram as a Predictor of Mortality in General Population.

Aro AL, Anttonen O, Tikkanen JT, Junttila MJ, ... Reunanen A, Huikuri HV
Background: -Prolonged duration of QRS complex (QRSd) in a 12-lead electrocardiogram (ECG) is associated with adverse prognosis in patients with cardiac disease, but its significance is not well established in general population. In particular, there is paucity of data on the prognostic significance of nonspecific intraventricular conduction delay (IVCD) in apparently healthy subjects. Methods and results: -We evaluated the 12-lead ECGs of 10899 Finnish middle-aged subjects from the general population (52% males, mean age 44±8.5 years) between 1966 and 1972 and followed them for 30±11 years. Primary end points were all-cause mortality, cardiac mortality, and arrhythmic death. Prolonged QRSd was defined as QRS ≥ 110 ms and IVCD as QRS ≥ 110 ms without the criteria of complete or incomplete bundle branch block. QRSd ≥ 110 ms was present in 1.3% (N=147) and IVCD in 0.6% (N=67) of the subjects. Prolonged QRSd predicted all-cause mortality (multivariate adjusted relative risk [RR] 1.48; 95% confidence interval [CI] 1.22-1.81; P<0.001), cardiac mortality (RR 1.94; CI 1.44-2.63; P<0.001), and sudden arrhythmic death (RR 2.14; CI 1.38-3.33; P=0.002). Subjects with IVCD had increased all-cause mortality (RR 2.01; CI 1.52-2.66; P<0.001), cardiac mortality (RR 2.53; CI 1.64-3.90; P<0.001), and an elevated risk of arrhythmic death (RR 3.11; CI 1.74-5.54; P=0.001). LBBB also weakly predicted arrhythmic death (P=0.04), but RBBB was not associated with increased mortality. Conclusions: -Prolonged QRSd in a standard 12-lead ECG is associated with increased mortality in general population, IVCD being most strongly associated with an increased risk of arrhythmic death.

Circ Arrhythm Electrophysiol: 15 Aug 2011; epub ahead of print
Aro AL, Anttonen O, Tikkanen JT, Junttila MJ, ... Reunanen A, Huikuri HV
Circ Arrhythm Electrophysiol: 15 Aug 2011; epub ahead of print | PMID: 21841194
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Abstract

Chest Compressions Cause Recurrence of Ventricular Fibrillation after the First Successful Conversion by Defibrillation in Out-of-Hospital Cardiac Arrest.

Berdowski J, Tijssen JG, Koster RW
Background: -Unlike Resuscitation Guidelines (GL) 2000, GL2005 advise resuming cardiopulmonary resuscitation (CPR) immediately after defibrillation. We hypothesized that immediate CPR resumption promotes earlier recurrence of ventricular fibrillation (VF). Methods and results: -This study used data of a prospective per-patient randomized controlled trial. Automated External Defibrillators (AEDs) used by first responders were randomized to either a) perform post-shock analysis and prompt rescuers to a pulse check - GL2000, or b) resume CPR immediately after defibrillation - GL2005. Continuous recordings of ECG and impedance signals were collected from all patients with an out-of-hospital cardiac arrest to whom a randomized AED was applied. We included patients with VF as their initial rhythm in whom CPR onset could be determined from the ECG and impedance signals. Time intervals are presented as median (Q1-to-Q3). Of 361 patients, 136 met the inclusion criteria: 68 were randomized to GL2000 and 68 to GL2005. Rescuers resumed CPR 30 (21-to-39) and 8 (7-to-9) seconds, respectively, after the first shock that successfully terminated VF (P<0.001); VF recurred after 40 (21-to-76) and 21 (10-to-80) seconds respectively (P=0.001). The time interval between start of CPR and VF recurrence was 6 (0-to-67) and 8 (3-to-61) seconds respectively (P=0.88). The hazard ratio for VF recurrence in the first 2 seconds of CPR was 15.5 (95% confidence interval, 5.63-57.7) compared to prior to CPR resumption. After more than 8 seconds of CPR, the hazard of VF recurrence was similar to prior to CPR resumption. Conclusions: -Early CPR resumption after defibrillation causes early VF recurrence. Clinical Trial registration Information-http://www.controlled-trials.com; Trial Number ISRCTN72257677.

Circ Arrhythm Electrophysiol: 31 Dec 2009; epub ahead of print
Berdowski J, Tijssen JG, Koster RW
Circ Arrhythm Electrophysiol: 31 Dec 2009; epub ahead of print | PMID: 20042768
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Abstract

Enhanced Dispersion of Repolarization Explains Increased Arrhythmogenesis in Severe vs. Therapeutic Hypothermia.

Piktel JS, Jeyaraj D, Said TH, Rosenbaum DS, Wilson LD
Background: -Hypothermia is proarrhythmic and as the use of therapeutic hypothermia (TH) increases, it is critically important to understand the electrophysiologic effects of hypothermia on cardiac myocytes and arrhythmia substrates. We tested the hypothesis that hypothermia-enhanced transmural dispersion of repolarization (DOR) is a mechanism of arrhythmogenesis in hypothermia. In addition, we investigated whether the degree of hypothermia, the rate of temperature change, and cooling vs. rewarming would alter hypothermia-induced arrhythmia substrates. Methods and results: -Optical action potentials were recorded from cells spanning the transmural wall of canine left ventricular wedge preparations at baseline (36°C), during cooling, and during rewarming. Electrophysiologic parameters were examined while varying the depth of hypothermia. Upon cooling to 26°C DOR increased from 26±4 ms to 93±18 ms (p=.021), conduction velocity (CV) decreased from 35±5 cm/s to 22±5 cm/s (p=.010). Upon rewarming to 36°C, DOR remained prolonged while CV returned to baseline. Conduction block and reentry was observed in all SH preparations. VF/VT was seen more during rewarming (4/5) vs. cooling (2/6). In TH (n=7), cooling to 32°;C mildly increased DOR (31±6 to 50±9, p=.012) with return to baseline upon rewarming and was associated with decreased arrhythmia susceptibility. Increased rate of cooling did not further enhance DOR or arrhythmogenesis. Conclusions: -Hypothermia amplifies DOR and is mechanism for arrhythmogenesis. DOR is directly dependent on the depth of cooling and rewarming. This provides insight into the clinical observation of a low incidence of arrhythmias in TH, and has implications for protocols for the clinical application of TH.

Circ Arrhythm Electrophysiol: 17 Dec 2010; epub ahead of print
Piktel JS, Jeyaraj D, Said TH, Rosenbaum DS, Wilson LD
Circ Arrhythm Electrophysiol: 17 Dec 2010; epub ahead of print | PMID: 21163888
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Abstract

SERCA2a Gene Transfer Decreases SR Calcium Leak and Reduces Ventricular Arrhythmias in a Model of Chronic Heart Failure.

Lyon AR, Bannister ML, Collins T, Pearce E, ... Macleod KT, Harding SE
Background: -Sarcoplasmic reticulum calcium ATPase 2a (SERCA2a) gene therapy improves mechanical function in heart failure, and is under evaluation in a clinical trial. A critical question is whether SERCA2a gene therapy predisposes to increased sarcoplasmic reticulum calcium (SR Ca(2+)) leak, cellular triggered activity and ventricular arrhythmias in the failing heart. Methods and results: -We studied the influence of SERCA2a gene therapy upon ventricular arrhythmogenesis in a rat chronic heart failure model. ECG telemetry studies revealed a significant antiarrhythmic effect of SERCA2a gene therapy with reduction of both spontaneous and catecholamine-induced arrhythmias in vivo. SERCA2a gene therapy also reduced susceptibility to reentry arrhythmias in ex vivo programmed electrical stimulation studies. Subcellular Ca(2+) homeostasis and spontaneous SR Ca(2+) leak characteristics were measured in failing cardiomyocytes transfected in vivo with a novel AAV9.SERCA2a vector. SR Ca(2+) leak was reduced following SERCA2a gene therapy, with reversal of the greater spark mass observed in the failing myocytes, despite normalisation of SR Ca(2+) load. SERCA2a reduced ryanodine receptor phosphorylation, thereby resetting SR Ca(2+) leak threshold, leading to reduced triggered activity in vitro. Both indirect effects of reverse remodelling and direct SERCA2a effects appear to underlie the antiarrhythmic action. Conclusions: -SERCA2a gene therapy stabilizes SR Ca(2+) load, reduces ryanodine receptor phosphorylation and decreases SR Ca(2+) leak, reduces cellular triggered activity in vitro and spontaneous and catecholamine-induced ventricular arrhythmias in vivo in failing hearts. SERCA2a gene therapy did not therefore predispose to arrhythmias, and may even represent a novel antiarrhythmic strategy in heart failure.

Circ Arrhythm Electrophysiol: 16 Mar 2011; epub ahead of print
Lyon AR, Bannister ML, Collins T, Pearce E, ... Macleod KT, Harding SE
Circ Arrhythm Electrophysiol: 16 Mar 2011; epub ahead of print | PMID: 21406682
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Abstract

Percutaneous Transatrial Access to the Pericardial Space for Epicardial Mapping and Ablation.

Scanavacca MI, Venancio AC, Pisani CF, Lara S, ... Mahapatra S, Sosa E
Background: -Puncture of the atrial appendage may provide access to the pericardial space. The aim of this study was to evaluate the feasibility of epicardial mapping and ablation through an endocardial transatrial access in a swine model. Methods and results: -An 8F Mullins sheath was used to perforate the right (16) or left (1) atrial appendage in 17 pigs with a median size of 27.5Kg (Q1 25.2, Q3 30.0 kg). A 7F ablation catheter was introduced into the pericardial space to perform epicardial mapping and deliver RF pulses on the atria. The pericardial space was entered in all 17 animals. In 15 (88%) animals there was no hemodynamic instability (mean BP monitoring: initial: median 80, Q1 70, Q3 86; final: median 88, Q1 80, Q3 96, p=0.426). In these 15, a mild hemorrhagic pericardial effusion was identified and aspirated (median: 20ml/animal; Q1 15, Q3 30 ml) during the procedure and post mortem gross analysis found the atrial perforation was closed in these animals. In 2 of 17 (12%) animals there was major pericardial bleeding with hemodynamic collapse. On gross examination it was found that pericardial space was accessed via right ventricular perforation in one animal and the tricuspid annulus in the other. After the initial study, we used an occlusion device in three other animals (SJM, St Paul MN) to attempt to seal the puncture (two at RAA and one at RV). These 3 animals had no significant pericardial bleeding. Conclusions: -Transatrial endovascular RAA puncture may provide a potential alternative route for pericardial access. Further studies are needed to evaluate its safety with longer and complexes procedures before being applied in clinical settings.

Circ Arrhythm Electrophysiol: 24 Mar 2011; epub ahead of print
Scanavacca MI, Venancio AC, Pisani CF, Lara S, ... Mahapatra S, Sosa E
Circ Arrhythm Electrophysiol: 24 Mar 2011; epub ahead of print | PMID: 21430128
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Abstract

Luminal Esophageal Temperature Monitoring with a Deflectable Esophageal Temperature Probe and Intracardiac Echocardiography May Reduce Esophageal Injury During Atrial Fibrillation Ablation Procedures - Results of a Pilot Study.

Leite LR, Santos SN, Maia H, Henz BD, ... d\'Avila A, Singh SM
Background: -Luminal esophageal temperature (LET) monitoring is one strategy to minimize esophageal injury during atrial fibrillation (AF) ablation procedures. However, esophageal ulceration and fistulas have been reported despite adequate LET monitoring. The objective of this study was to assess a novel approach to LET monitoring with a deflectable LET probe on the rate of esophageal injury in patients undergoing AF ablation. Methods and results: -45 consecutive patients undergoing an AF ablation procedure followed by esophageal endoscopy were included in this prospective observational pilot study. LET monitoring was performed with a 7Fr deflectable ablation catheter which was positioned as close as possible to the site of left atrial (LA) ablation using the deflectable component of the catheter guided by visualization of its position on intra-cardiac echocardiography (ICE). Ablation in the posterior LA was limited to 25 Watts, and terminated when the LET increased 2°C from baseline. Endoscopy was performed 1-2 days post-procedure. All patients experienced at least one LET elevation >2°C necessitating cessation of ablation. Deflection of the LET probe was needed to accurately measure LET in 5% of patients when ablating near the left pulmonary veins (PVs) whereas deflection of the LET probe was necessary in 88% of patients when ablating near the right PVs. The average maximum increase in LET was 2.5±1.5°C. No patients had esophageal thermal injury on follow-up endoscopy. Conclusions: -A strategy of optimal LET probe placement using a deflectable LET probe and ICE guidance, combined with cessation of RF ablation with a 2°C rise in LET, may reduce esophageal thermal injury during AF ablation procedures.

Circ Arrhythm Electrophysiol: 17 Feb 2011; epub ahead of print
Leite LR, Santos SN, Maia H, Henz BD, ... d'Avila A, Singh SM
Circ Arrhythm Electrophysiol: 17 Feb 2011; epub ahead of print | PMID: 21325208
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Abstract

A Novel Lead Configuration for Optimal Spatio-Temporal Detection of Intracardiac Repolarization Alternans.

Weiss EH, Merchant FM, d\'Avila A, Foley L, ... Ruskin JN, Armoundas AA
Background: -Electrical alternans is a pattern of variation in the shape of electrocardiographic waveform that occurs every other beat. In humans, alternation in ventricular repolarization, known as repolarization alternans (RA), has been associated with increased vulnerability to ventricular tachycardia/fibrillation and sudden cardiac death. Methods and results: -This study investigates the spatio-temporal variability of intracardiac RA and its relationship to body surface RA in an acute myocardial ischemia model in swine. We developed a real-time multi-channel repolarization signal acquisition, display and analysis system to record electrocardiographic signals from catheters in the right ventricle, coronary sinus, left ventricle, and epicardial surface prior to and following circumflex coronary artery balloon occlusion. We found that RA is detectable within 4 minutes following the onset ischemia, and is most prominently seen during the first half of the repolarization interval. Ischemia-induced RA was detectable on unipolar and bipolar leads (both in near- and far-field configurations) and on body surface leads. Far-field bipolar intracardiac leads were more sensitive for RA detection than body surface leads, with the probability of body surface RA detection increasing as the number of intracardiac leads detecting RA increased, approaching 100% when at least three intracardiac leads detected RA. We developed a novel, clinically-applicable intracardiac lead system based on a triangular arrangement of leads spanning the right ventricular (RV) and coronary sinus (CS) catheters which provided the highest sensitivity for intracardiac RA detection when compared to any other far-field bipolar sensing configurations (p < 0.0001). Conclusions: -In conclusion, intracardiac alternans, a complex spatio-temporal phenomenon associated with arrhythmia susceptibility and sudden cardiac death, can be reliably detected through a novel triangular RV-CS lead configuration.

Circ Arrhythm Electrophysiol: 24 Mar 2011; epub ahead of print
Weiss EH, Merchant FM, d'Avila A, Foley L, ... Ruskin JN, Armoundas AA
Circ Arrhythm Electrophysiol: 24 Mar 2011; epub ahead of print | PMID: 21430127
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Abstract

Clinical Characteristics and Long-Term Prognosis of Vasospastic Angina Patients Who Survived Out-of-Hospital Cardiac Arrest: Multicenter Registry Study of the Japanese Coronary Spasm Association.

Takagi Y, Yasuda S, Tsunoda R, Ogata Y, ... Ogawa H, Shimokawa H
Background: -Coronary artery spasm plays an important role in the pathogenesis of ischemic heart disease; however, its role in sudden cardiac death remains to be fully elucidated. We examined the clinical characteristics and outcomes of patients with vasospastic angina (VSA) in our nationwide multicenter registry by the Japanese Coronary Spasm Association. Methods and results: -Between September 2007 and December 2008, 1,429 patients with VSA (M/F, 1,090/339: median 66 years) were identified. They were characterized by a high prevalence of smoking and included 35 patients who survived out-of-hospital cardiac arrest (OHCA). The OHCA survivors, as compared with the remaining 1,394 non-OHCA patients, were characterized by younger age (median 58 vs. 66 years, P<0.001) and higher incidence of left anterior descending coronary artery spasm (72 vs. 53%, P<0.05). In the OHCA survivors, 14 patients underwent implantable cardioverter defibrillator (ICD) implantation while intensively treated with calcium channel blockers. Survival rate free from major adverse cardiac events (MACE) was significantly lower in the OHCA survivors compared with the non-OHCA patients (72 vs. 92% at 5 years, P<0.001), including appropriate ICD shocks for ventricular fibrillation in 2 patients. Multivariable analysis revealed that OHCA event was significantly correlated with MACE (hazard ratio, 3.25; 95% confidence interval, 1.39 to 7.61; P<0.01). Conclusions: -These results from the largest VSA cohort indicate that vasospasm patients who survived OHCA are high risk population. Further studies are needed to determine whether ICD therapy improves the patients\' prognosis.

Circ Arrhythm Electrophysiol: 16 Mar 2011; epub ahead of print
Takagi Y, Yasuda S, Tsunoda R, Ogata Y, ... Ogawa H, Shimokawa H
Circ Arrhythm Electrophysiol: 16 Mar 2011; epub ahead of print | PMID: 21406685
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Abstract

Dynamically Shaped Magnetic Fields: Initial Animal Validation of a New Remote Electrophysiology Catheter Guidance and Control System.

Gang ES, Nguyen BL, Shachar Y, Farkas L, ... Gaudio C, Kim SJ
Background: -To address some of the shortcomings of existing remote catheter navigation systems (RNS), a new magnetic RNS has been developed which provides real-time navigation of catheters within the beating heart. The initial experience using this novel RNS in animals is described herein. Methods and results: -A real-time, high-speed, closed loop, magnetic RNS system (Catheter Guidance Control and Imaging, CGCI) is comprised of eight electromagnets that create unique dynamically shaped ("lobed") magnetic fields around the subject\'s torso. The real-time reshaping of these magnetic fields produces the appropriate three-dimensional motion or change in direction of a magnetized electrophysiology ablation catheter within the beating heart. The RNS is fully integrated with the Ensite-NavX(TM) three-dimensional electroanatomic mapping system (St. Jude Medical), and allows for both joystick and automated navigation. Conventional and remote navigational mapping of the left atrium were performed using a 4-mm tip ablation catheter in 10 pigs. A multielectrode transseptal sheath allowed for additional motion compensation. Linear and circumferential radiofrequency lesion sets were performed; in a subset of cases, selective pulmonary vein isolation was also performed. Recording and fluoroscopic equipments were unaffected by the magnetic fields generated by CGCI. Automated mode navigation was highly reproducible (96±8.4% of attempts), accurate (1.9±0.4 mm from target site), and rapid (11.6±3.5 sec to reach targets). At post-mortem, radiofrequency lesion depth was 78.5±12.1% of atrial wall thickness. Conclusions: -A new magnetic RNS using a dynamically shaped magnetic field concept can reproducibly and effectively reach target RF ablation points within the pig left atrium. Validation of the system in clinical settings is under way.

Circ Arrhythm Electrophysiol: 21 Jun 2011; epub ahead of print
Gang ES, Nguyen BL, Shachar Y, Farkas L, ... Gaudio C, Kim SJ
Circ Arrhythm Electrophysiol: 21 Jun 2011; epub ahead of print | PMID: 21690463
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Abstract

Early Repolarization Pattern in Competitive Athletes: Clinical Correlates and the Effects of Exercise Training.

Noseworthy PA, Weiner R, Kim J, Keelara V, ... Newton-Cheh C, Baggish AL
Background: -Inferior lead early repolarization pattern (ERP) has recently been associated with sudden cardiac death. Although ERP is common among athletes, prevalence, ECG lead distribution, clinical characteristics, and effects of physical training remain uncertain. We sought to examine the non-anterior early repolarization pattern (ERP) in competitive athletes. Methods and results: -ERP was assessed in a cross-sectional cohort of collegiate athletes (n=879). The relationship between ERP and cardiac structure were then examined in a longitudinal subgroup (n=146) before and after a 90-day period of exercise training. ERP was defined as J-point elevation ≥ 0.1 mV in at least two leads within a non-anterior territory (inferior [II, III, aVF] or lateral [I, aVL, V4-V6]). Non-anterior ERP was present in 25.1% (221/879) of athletes including the inferior subtype in 3.8% (33/879). Exercise training led to significant increases in the prevalence of ERP and the inferior subtype but there were no associations between ERP and echocardiographic measures of left ventricular remodeling. In a multivariable model, ERP was associated with black race (OR 5.84, CI 3.54-9.61, p<0.001), increased QRS voltage (OR 2.08, CI 1.71-2.52, p<0.001), and slower HR (OR 1.54, CI 1.26-1.87, p<0.001). Conclusions: -Non-anterior ERP including the inferior subtype are common and have strong clinical associations among competitive athletes. The finding of increased ERP prevalence following intense physical training establishes a strong association between exercise and the ERP.

Circ Arrhythm Electrophysiol: 05 May 2011; epub ahead of print
Noseworthy PA, Weiner R, Kim J, Keelara V, ... Newton-Cheh C, Baggish AL
Circ Arrhythm Electrophysiol: 05 May 2011; epub ahead of print | PMID: 21543642
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Abstract

Safety of Pacemaker Reutilization: A Meta-Analysis with Implications for Underserved Nations.

Baman TS, Meier P, Romero J, Gakenheimer L, ... Oral H, Eagle KA
Background: -A large disparity in medical healthcare is clearly evident between developed and underserved nations in the field of cardiac electrophysiology - specifically pacemaker implantation. This study aimed to assess the safety of pacemaker reutilization. Methods and results: -A computerized search from January 1(st) 1970 to September 1(st) 2010 identified 18 studies with outcomes of pacemaker reutilization. The primary outcome was pacemaker infection or device erosion as defined by each individual study protocol. Secondary endpoints were device malfunction defined as a defect in the structural or electrical integrity of the pulse generator. Pooled individual patient data (n=2,270) from 18 trials were included in the analysis. The proportion of patients who developed an infection after pacemaker reutilization was 1.97% [1.15 to 3.00%]. There was no significant difference in infection rate between pacemaker reutilization and new device implantation, OR 1.31 [0.50 to 3.40], p=0.580. The proportion of patients who developed device malfunction after pacemaker reutilization was 0.68% [0.27 to 1.28%]. Compared with new device implantation, there was an increased risk for malfunction in the reuse group, OR 5.80 [1.93 to 17.47], p= 0.002. This difference was mainly driven by abnormalities in set screws which possibly occurred during device extraction as well as nonspecific device "technical errors." Conclusions: -This study would suggest that pacemaker reutilization has an overall low rate of infection and device malfunction and may be a safe and efficacious means of treating patients in underserved nations with symptomatic bradyarrhythmias and no other method of obtaining a device. However, the results also denote a higher rate of device malfunction as compared to new device implantation. Patients with highly symptomatic conduction disease may benefit from pacemaker reutilization; however, they should be closely monitored for device malfunction especially during implantation.

Circ Arrhythm Electrophysiol: 15 Apr 2011; epub ahead of print
Baman TS, Meier P, Romero J, Gakenheimer L, ... Oral H, Eagle KA
Circ Arrhythm Electrophysiol: 15 Apr 2011; epub ahead of print | PMID: 21493963
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Abstract

Autonomic Remodeling in the Left Atrium and Pulmonary Veins in Heart Failure - Creation of a Dynamic Substrate for Atrial Fibrillation.

Ng J, Villuendas R, Cokic I, Schliamser JE, ... Aistrup GL, Arora R
Background: -Atrial fibrillation (AF) is commonly associated with congestive heart failure (CHF). The autonomic nervous system is involved in the pathogenesis of both AF and CHF. We examined the role of autonomic remodeling in contributing to AF substrate in CHF. Methods and results: -Electrophysiological mapping was performed in the pulmonary veins (PVs) and left atrium (LA) in 38 rapid-ventricular paced dogs (CHF group) and 39 controls under the following conditions: vagal stimulation, isoproterenol infusion, β-adrenergic blockade, acetylcholinesterase (AChE) inhibition (physostigmine), parasympathetic blockade, and double autonomic blockade. Explanted atria were examined for nerve density/distribution, muscarinic receptor (MR) and beta-adrenergic receptor (βAR) densities, and AChE activity. In CHF dogs, there was an increase in nerve bundle size, parasympathetic fibers/bundle, and density of sympathetic fibrils and cardiac ganglia, all preferentially in the posterior LA/PVs. Sympathetic hyperinnervation was accompanied by increases in β(1)AR density and in sympathetic effect on ERPs and activation direction. β-adrenergic blockade slowed AF dominant frequency. Parasympathetic remodeling was more complex, resulting in increased AChE activity, unchanged MR density, unchanged parasympathetic effect on activation direction, and decreased effect of vagal stimulation on ERP (restored by AChE inhibition). Parasympathetic blockade markedly decreased AF duration. Conclusions: -In this heart failure model autonomic and electrophysiologic remodeling occurs involving the posterior left atrium and pulmonary veins. Despite synaptic compensation, parasympathetic hyperinnervation contributes significantly to AF maintenance. Parasympathetic and/or sympathetic signaling may be possible therapeutic targets for AF in CHF.

Circ Arrhythm Electrophysiol: 22 Mar 2011; epub ahead of print
Ng J, Villuendas R, Cokic I, Schliamser JE, ... Aistrup GL, Arora R
Circ Arrhythm Electrophysiol: 22 Mar 2011; epub ahead of print | PMID: 21421805
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Abstract

Natural History and Long Term Outcomes of Ablated Atrial Fibrillation.

Hussein AA, Saliba WI, Martin DO, Bhargava M, ... Natale A, Wazni O
Background: -Atrial fibrillation (AF) ablation is increasingly used in clinical practice. We aimed to study the natural history and long term outcomes of ablated AF. Methods and results: -We followed 831 patients after pulmonary vein isolation (PVI) performed in 2005. We documented clinical outcomes using our prospective AF registry with most recent update on this group of patients in October 2009. In the first year after ablation, 23.8% had early recurrence. Over long term follow-up (55 months), only 8.9% had late arrhythmia recurrence defined as occurring beyond the first year post ablation. Repeat ablations in patients with late recurrence revealed conduction recovery in at least one of the previously isolated PVs in all of them and right sided triggers with Isoproterenol testing in 55.6%. At last follow-up, clinical improvement was 89.9% (79.4% arrhythmia free off antiarrhythmics and 10.5% with AF controlled with antiarrhythmics). Only 4.6% continued to have drug resistant AF. It was possible to safely discontinue anticoagulation in a substantial proportion of patients with no recurrence in the year after ablation (CHADS score ≤ 2, stroke incidence of 0.06%/year). The procedure-related complication rate was very low. Conclusions: -PVI is safe and efficacious for long term maintenance of sinus rhythm and control of symptoms in patients with drug resistant AF. It obviates the need for antiarrhythmics, negative dromotropic agents and anticoagulants in a substantial proportion of patients.

Circ Arrhythm Electrophysiol: 15 Apr 2011; epub ahead of print
Hussein AA, Saliba WI, Martin DO, Bhargava M, ... Natale A, Wazni O
Circ Arrhythm Electrophysiol: 15 Apr 2011; epub ahead of print | PMID: 21493959
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Abstract

Entrainment for Distinguishing Atypical AVNRT from AVRT over Septal Accessory Pathways with Long RP Tachycardia.

Bennett MT, Leong-Sit P, Gula LJ, Skanes AC, ... Hogg EC, Klein GJ
Background: -The response to right ventricular (RV) entrainment is useful to distinguish atypical AV node reentrant tachycardia (AVNRT) from atrio-ventricular reentrant tachycardia (AVRT) using a septal accessory pathway. Whether this can differentiate between AVNRT and AVRT in patients with long RP tachycardia has not been systematically validated. Methods and results: -Twenty-four patients with concealed septal accessory pathways who had an electrophysiology study between January 1, 2000 and January 1, 2010 were included (age 38±17, 17 male). Entrainment was performed from the RV apex pacing at cycle length 20-40 ms shorter than tachycardia cycle length (TCL). The mean tachycardia cycle length was 390±80 msec, the mean A-H interval during tachycardia was 151±57 msec and the mean V-A time was 182±103 msec. Twelve patients had typical accessory pathways (VA/TCL<40%) and twelve patients had slowly conducting accessory pathways (VA/TCL≥40%). In all patients with typical accessory pathways, the post-pacing interval minus the tachycardia cycle length (PPI-TCL) was less than 115 msec and the stim A-VA was less than 85 msec. On the other hand, in 6 of the 12 patients in the slowly conducting group, the PPI-TCL was greater than 115msec and the stim A-VA was greater than 85msec. Conclusions: -Slowly conducting accessory pathways frequently yield RV entrainment criteria traditionally attributable to AV node reentry. Distinguishing AV node reentry from AV reentry in patients with long RP tachycardia requires other criteria.

Circ Arrhythm Electrophysiol: 03 Jun 2011; epub ahead of print
Bennett MT, Leong-Sit P, Gula LJ, Skanes AC, ... Hogg EC, Klein GJ
Circ Arrhythm Electrophysiol: 03 Jun 2011; epub ahead of print | PMID: 21636810
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Abstract

Effect of Right Ventricular Versus Biventricular Pacing on Electrical Remodeling in the Normal Heart.

Saba S, Mehdi H, Mathier MA, Islam MZ, Salama G, London B
Background: -Biventricular (BIV) pacing can improve cardiac function in heart failure by altering the mechanical and electrical substrates. We investigated the effect of BIV versus right ventricular (RV) pacing on the normal heart. Methods and results: -Male New Zealand White rabbits (n=33) were divided into 3 groups: sham-operated (control), RV pacing, and BIV pacing groups. Four weeks after surgery, the native QT (p=0.004) interval was significantly shorter in the BIV group compared to the RV or sham-operated groups. Also, compared to rabbits in the RV group, rabbits in the BIV group had shorter RV ventricular effective refractory period (VERP) at all cycle lengths, and shorter LV paced QT interval during the drive train of stimuli and close to refractoriness (p<0.001 for all comparisons). Protein expression of the KVLQT1 was significantly increased in the BIV group compared to the RV and control groups, while protein expression of SCN5A and connexin43 was significantly decreased in the RV compared to the other study groups. Erg protein expression was significantly increased in both pacing groups compared to the controls. Conclusions: -In this rabbit model, we demonstrate a direct effect of BIV but not RV pacing on shortening the native QT interval as well as the paced QT interval during burst pacing and close to the VERP. These findings underscore the fact that the effect of BIV pacing is partially mediated through direct electrical remodeling and may have implications as to the effect of BIV pacing on arrhythmia incidence and burden.

Circ Arrhythm Electrophysiol: 31 Dec 2009; epub ahead of print
Saba S, Mehdi H, Mathier MA, Islam MZ, Salama G, London B
Circ Arrhythm Electrophysiol: 31 Dec 2009; epub ahead of print | PMID: 20042767
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Abstract

Spontaneous Ventricular Fibrillation in Right Ventricular Failure Secondary to Chronic Pulmonary Hypertension.

Umar S, Lee JH, de Lange E, Iorga A, ... Karagueuzian HS, Eghbali M
Background: -Right ventricular failure (RVF) in pulmonary hypertension (PH) is associated with increased incidence of sudden death by a poorly explored mechanism. Here we test the hypothesis that PH promotes spontaneous ventricular fibrillation (VF) during a critical post-PH onset period characterized by a sudden increase in mortality. Methods and results: -Rats received either a single subcutaneous dose of monocrotaline (MCT, 60 mg/kg) to induce PH-associated RVF (PH, n=24) or saline (CTRL, n=17). Activation pattern of RV-epicardial surface was mapped using voltage-sensitive dye in isolated Langendorff-perfused hearts along with single glass-microelectrode and ECG-recordings. MCT-injected rats developed severe PH by day-21 and progressed to RVF by ~day-30. Rats manifested increased mortality and ~30% rats died suddenly and precipitously during 23-32 days post-MCT. This fatal period was associated with the initiation of spontaneous VF by a focal mechanism in the RV which was subsequently maintained by both focal and incomplete re-entrant wavefronts. Microelectrode recordings from the RV-epicardium at the onset of focal activity showed early afterdepolarization (EAD)-mediated triggered activity that led to VF. The onset of the RV cellular triggered beats preceded left ventricular depolarizations by 23±8 ms. The RV but not the LV cardiomyocytes isolated during this fatal period manifested significant action potential duration prolongation, dispersion and an increased susceptibility to depolarization-induced repetitive activity. No spontaneous VF was observed in any of the CTRL hearts. RVF was associated with significantly reduced RV ejection fraction (p<0.001), RV hypertrophy (p<0.001) and RV fibrosis (p<0.01). The hemodynamic function of the LV and its structure were preserved. Conclusions: -PH-induced RVF is associated with a distinct phase of increased mortality characterized by spontaneous VF arising from the RV by an EAD-mediated triggered activity.

Circ Arrhythm Electrophysiol: 26 Dec 2011; epub ahead of print
Umar S, Lee JH, de Lange E, Iorga A, ... Karagueuzian HS, Eghbali M
Circ Arrhythm Electrophysiol: 26 Dec 2011; epub ahead of print | PMID: 22199010
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Abstract

Genesis of Phase-3 Early Afterdepolarizations and Triggered Activity in Acquired Long QT Syndrome.

Maruyama M, Lin SF, Xie Y, Chua SK, ... Weiss JN, Chen PS
Background: -Both phase-2 and phase-3 early afterdepolarizations (EADs) occur in long QT syndromes, but their respective roles in generating arrhythmias in intact cardiac tissue are incompletely understood. Methods and results: -Intracellular Ca (Ca(i)) and membrane voltage (V(m)) were optically mapped in a quasi 2-dimensional model of cryoablated Langendorff-perfused rabbit ventricles (n = 16). E-4031 (an I(Kr) blocker) combined with reduced extracellular K ([K(+)](o)) and Mg ([Mg(2+)](o)) prolonged action potential duration (APD) heterogeneously and induced phase-2 and phase-3 EADs. While phase-2 EADs were Ca(i)-dependent, phase-3 EADs were not. The origins of 47 triggered activity (TA) episodes were attributed to phase-2 EADs in 12 episodes (26%) and phase-3 EADs in 35 episodes (74%). When phase-2 EADs accompanied phase-3 EADs, they accentuated APD heterogeneity, creating a large V(m) gradient across the boundary between long and short APD regions from which TA emerged. The amplitude of phase-3 EADs correlated with the V(m) gradient (r = 0.898, P < 0.001). Computer simulation studies showed that coupling of cells with heterogeneous repolarization could extrinsically generate phase-3 EADs via electrotonic current flow. Alternatively, reduced I(K1) caused by low [K(+)](o) could generate intrinsic phase-3 EADs capable of inducing TA at the boundary zone. Conclusions: -Phase-3 EADs can be extrinsic due to electrotonic current across steep repolarization gradients, or intrinsic due to low I(K1), and do not require spontaneous sarcoplasmic reticulum Ca release. Reduction of I(K1) by low [K(+)](o) strongly promotes ventricular arrhythmias mediated by phase-3 EADs in acquired long QT syndrome due to I(Kr) blockade.

Circ Arrhythm Electrophysiol: 16 Nov 2010; epub ahead of print
Maruyama M, Lin SF, Xie Y, Chua SK, ... Weiss JN, Chen PS
Circ Arrhythm Electrophysiol: 16 Nov 2010; epub ahead of print | PMID: 21078812
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Abstract

Cardiac Sarcoidosis and Giant Cell Myocarditis as Causes of Atrioventricular Block in Young and Middle-Aged Adults.

Kandolin R, Lehtonen J, Kupari M
Background: -Cardiac sarcoidosis (CS) and giant cell myocarditis (GCM) may present as high-degree atrioventricular block (AVB) but their proportion of the causal spectrum of AVB is not well known. We investigated the prevalence of biopsy-verified CS and GCM in young and middle-aged adults undergoing pacemaker (PM) implantation for AVB. Methods and results: -We used the PM registry of Helsinki University Central Hospital to identify all patients aged 18-55 years who underwent PM implantation for AVB between 1/99 and 4/09 and reviewed their medical records. Totally 133 patients had either 2(nd) or 3(rd) degree AVB as an indication for PM. Of them, 61 had a known cause for AVB; they were excluded from further analyses. Among the remaining 72 patients with initially unexplained AVB, biopsy-verified CS or GCM was found in 14 (19%) and 4 (6%) patients, respectively. The majority of them (16/18, 89%) were women. Among the adult patients aged under 55 years, the prevalence of CS and GCM combined was 14 % (95% CI 7.7-19.3) of the whole AVB population and 25 % (95% CI 15-35) of those with an initially unexplained AVB. Over an average of 48 months of follow-up, 7 of 18 patients with CS or GCM (39 %), versus 1 of the 54 patients in whom AVB remained idiopathic, experienced either cardiac death, cardiac transplantation, ventricular fibrillation, or treated sustained ventricular tachycardia (p<0.001). Conclusions: -CS and GCM explain at least 25 % of initially unexplained AVB in young and middle-aged adults. These patients are at high risk of adverse cardiac events.

Circ Arrhythm Electrophysiol: 23 Mar 2011; epub ahead of print
Kandolin R, Lehtonen J, Kupari M
Circ Arrhythm Electrophysiol: 23 Mar 2011; epub ahead of print | PMID: 21427276
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Abstract

Direct Measurement of the Lethal Isotherm for Radiofrequency Ablation of Myocardial Tissue.

Wood M, Goldberg S, Lau M, Goel A, ... Han F, Feinstein S
Background: -The lethal isotherm for radiofrequency (RF) catheter ablation of cardiac myocardium is widely accepted to be 50°C but this has not been directly measured. The purpose of this study was to directly measure the tissue temperature at the edge of RF lesions in real time using infrared thermal imaging. Methods and results: -Fifteen radiofrequency lesions of 6 - 240 seconds in duration were applied to the left ventricular surface of isolated perfused pig hearts. At the end of RF delivery, a thermal image of the tissue surface was acquired with an infrared camera. The lesion was then stained and an optical image of the lesion was obtained. The thermal and optical images were electronically merged to allow determination of the tissue temperature at the edge of the lesion at the end of RF delivery. By adjusting the temperature overlay display to conform with the edge of the RF lesion, the lethal isotherm was measured to be 60.6°C (interquartile ranges 59.7, 62.4°C, range 58.1 - 64.2°C). The areas encompassed by the lesion border in the optical image and the lethal isotherm in the thermal image were statistically similar and highly correlated (Spearman\'s rho = 0.99, p <0.001). The lethal isotherm temperature was not related to the duration of RF delivery or to lesion size (both p ≥ 0.64). The areas circumscribed by 50°C isotherms were significantly larger than the areas of the lesions on optical imaging (p = 0.002). Conclusions: -By direct measurement, the lethal isotherm for cardiac myocardium is near 61°C for RF energy deliveries ≤ 240 seconds in duration. A 50°C isotherm overestimates lesion size. Accurate knowledge of the lethal isotherm for RF ablation is important to clinical practice as well as mathematical modeling of RF lesions.

Circ Arrhythm Electrophysiol: 16 Mar 2011; epub ahead of print
Wood M, Goldberg S, Lau M, Goel A, ... Han F, Feinstein S
Circ Arrhythm Electrophysiol: 16 Mar 2011; epub ahead of print | PMID: 21406684
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Abstract

Common Variants in Cardiac Ion Channel Genes Are Associated with Sudden Cardiac Death.

Albert CM, Macrae CA, Chasman DI, Vandenburgh M, ... Cook NR, Newton-Cheh CH
Background: -Rare variants in cardiac ion channel genes are associated with sudden cardiac death (SCD) in rare primary arrhythmic syndromes; however, it is unknown whether common variation in these same genes may contribute to SCD risk at the population level. Methods and results: -We examined the association between 147 single nucleotide polymorphisms (SNPs) (137 tag, 5 non-coding SNPs associated with QT interval duration and 5 nonsynonymous SNPs) in 5 cardiac ion channel genes, KCNQ1, KCNH2, SCN5A, KCNE1 and KCNE2 and sudden and/or arrhythmic death in a combined nested case-control analysis among 516 cases and 1522 matched controls of European ancestry enrolled in six prospective cohort studies. After accounting for multiple testing, two SNPs (rs2283222 located in intron 11 in KCNQ1 and rs11720524 located in intron 1 in SCN5A) remained significantly associated with sudden/arrhythmic death (FDR = 0.01 and 0.03 respectively). Each increasing copy of the major T allele of rs2283222 or the major C allele of rs1172052 was associated with an OR = 1.36 (95% CI 1.16-1.60, P=0.0002) and 1.30 (95% CI 1.12-1.51, P=0.0005) respectively. Control for cardiovascular risk factors and/or limiting the analysis to definite SCDs did not significantly alter these relationships. Conclusions: -In this combined analysis of 6 prospective cohort studies, two common intronic variants in KCNQ1 and SCN5A were associated with SCD in individuals of European ancestry. Further study in other populations and investigation into the functional abnormalities associated with non-coding variation in these genes may lead to important insights into predisposition to lethal arrhythmias.

Circ Arrhythm Electrophysiol: 19 Apr 2010; epub ahead of print
Albert CM, Macrae CA, Chasman DI, Vandenburgh M, ... Cook NR, Newton-Cheh CH
Circ Arrhythm Electrophysiol: 19 Apr 2010; epub ahead of print | PMID: 20400777
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Abstract

Low Atrial Fibrillatory Rate Is Associated with Poor Outcome in Patients with Mild to Moderate Heart Failure.

Platonov PG, Cygankiewicz I, Stridh M, Holmqvist F, ... Zareba W, Bayes de Luna A
Background: -Atrial fibrillatory rate (AFR) is a measure of atrial remodeling caused by atrial fibrillation (AF) and its acceleration negatively affects outcome of interventions for persistent AF. However, the prognostic value of AFR in patients with CHF has not been studied. We sought to evaluate whether AFR can predict outcome in patients with mild to moderate (NYHA II-III) congestive heart failure (CHF). Methods and results: -High-resolution 20-min long Holter ECGs obtained from 169 CHF patients with AF at enrollment were analyzed. AFR was estimated using spatiotemporal QRST cancellation and time-frequency analysis. The patients were followed for a median of 44 months with primary endpoint defined as total mortality and secondary endpoints as sudden death and heart failure death. Atrial signal quality was sufficient for AFR estimation in 142 patients (mean age 69±11 years, 101 male). Of those, 48 patients died during follow-up, including 18 due to CHF progression. Mean AFR was 390±60 fpm and decreased with age (r=-0.3, p<0.001). Patients with AFR≤371 fpm (lower tertile) had 44% 3-year mortality as compared to 26% with higher AFR. Lower AFR was an independent predictor of all cause mortality (HR=1.99, 95% CI=1.09-3.63, p=0.025) and CHF death (HR=3.74, 95% CI=1.38-10.14, p=0.010) after adjustment for significant clinical covariates in multivariable Cox analysis. Conclusions: -In CHF patients with AF, reduced AFR assessed using non-invasive approach is associated with increased risk of death due to heart failure progression and may be considered as a predictor of outcome.

Circ Arrhythm Electrophysiol: 11 Jan 2012; epub ahead of print
Platonov PG, Cygankiewicz I, Stridh M, Holmqvist F, ... Zareba W, Bayes de Luna A
Circ Arrhythm Electrophysiol: 11 Jan 2012; epub ahead of print | PMID: 22235036
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Abstract

The Extent of Left Ventricular Scar Quantified by Late Gadolinium Enhancement MRI Is Associated with Spontaneous Ventricular Arrhythmias in Patients with Coronary Artery Disease and Implantable Cardioverter Defibrillators.

Scott PA, Morgan JM, Carroll N, Murday DC, ... Harden SP, Curzen NP
Background: -Characterization of sudden cardiac death (SCD) risk remains a challenge in the application of implantable cardioverter defibrillator (ICD) therapy. Late gadolinium enhancement cardiac magnetic resonance imaging (LGE-CMR) can accurately identify myocardial scar. We performed a retrospective single centre observational study, evaluating the association between the extent and distribution of LV scar, quantified using LGE-CMR, and the burden of ventricular arrhythmias, in patients with coronary artery disease and ICDs. Methods and results: -All patients included (2006-2009) had undergone LGE-CMR prior to ICD implantation. Scar (defined as myocardium with a signal intensity ≥50% of the maximum in scar tissue) was characterised in terms of percent scar, scar surface area, and number of transmural LV scar segments. The end-point was appropriate ICD therapy. Sixty-four patients (average age 66±11 years, 51 male) were included. During 19±10 months follow-up, appropriate ICD therapy occurred in 19 patients (30%). In Cox regression analyses both percent scar (hazard ratio [HR] per 10% 1.75; 95% confidence intervals [CI] 1.09-2.81; p=0.02) and number of transmural scar segments (HR per segment 1.40; 95% CI 1.15-1.70; p=0.001), were significantly associated with the occurrence of appropriate ICD therapy. Conclusions: -In this pilot study, the extent of myocardial scar, characterised by LGE-CMR, was significantly associated with the occurrence of spontaneous ventricular arrhythmias. We hypothesise that scar quantification by LGE-CMR may prove a valuable risk stratification tool for the occurrence of ventricular arrhythmias, which may have implications for patient selection for ICD therapy.

Circ Arrhythm Electrophysiol: 15 Apr 2011; epub ahead of print
Scott PA, Morgan JM, Carroll N, Murday DC, ... Harden SP, Curzen NP
Circ Arrhythm Electrophysiol: 15 Apr 2011; epub ahead of print | PMID: 21493964
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Abstract

Vernakalant hydrochloride for the rapid conversion of atrial fibrillation after cardiac surgery: a randomized, double-blind, placebo-controlled trial.

Kowey PR, Dorian P, Mitchell LB, Pratt CM, ... Toft E,
Background: Postoperative atrial arrhythmias are common and are associated with considerable morbidity. This study was designed to evaluate the efficacy and safety of vernakalant for the conversion of atrial fibrillation (AF) or atrial flutter (AFL) after cardiac surgery. Methods and results: This was a prospective, randomized, double-blind, placebo-controlled trial of vernakalant for the conversion of AF or AFL after coronary artery bypass graft, valvular surgery, or both. Patients were randomly assigned 2:1 to receive a 10-minute infusion of 3 mg/kg vernakalant or placebo. If AF or AFL was present after a 15-minute observation period, then a second 10-minute infusion of 2 mg/kg vernakalant or placebo was given. The primary end point was the conversion of postcardiac surgery AF or AFL to sinus rhythm within 90 minutes of dosing. In patients with AF, 47 of 100 (47%) who received vernakalant converted to SR compared with 7 of 50 (14%) patients who received placebo (P<0.001). The median time to conversion was 12 minutes. Vernakalant was not effective in converting postoperative AFL to sinus rhythm. Two serious adverse events occurred within 24 hours of vernakalant administration (hypotension and complete atrioventricular block). There were no cases of torsades de pointes, sustained ventricular tachycardia, or ventricular fibrillation. There were no deaths. Conclusions: Vernakalant was safe and effective in the rapid conversion of AF to sinus rhythm in patients who had AF after cardiac surgery. Clinical trial registration: clinicaltrials.gov. Identifier: NCT00125320.

Circ Arrhythm Electrophysiol: 16 Dec 2009; 2:652-9
Kowey PR, Dorian P, Mitchell LB, Pratt CM, ... Toft E,
Circ Arrhythm Electrophysiol: 16 Dec 2009; 2:652-9 | PMID: 19948506
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Abstract

Coexistence of Left Sided Atrioventricular Accessory Pathways with a Common Inferior Pulmonary Vein Ostium.

Ihara K, Nitta J, Sato A, Iwai S, ... Hirao K, Isobe M
Background: -As the technique for radiofrequency catheter ablation for atrial fibrillation (AF) has progressed, so has our knowledge of both normal and abnormal anatomy of the left atrium and pulmonary veins (PV). We treated several AF patients with accessory conduction pathways (ACP) who were also found to have a common ostium of inferior PVs (CIPV), a relatively rare PV anomaly. No relation between ACP and PV anomalies has ever been reported, and the aim of our study was to study this association. Methods and results: -This study included 137 consecutive patients (104 men, mean age 60±9 years) who underwent AF ablation for paroxysmal and persistent AF at our institution, from March 2009 to August 2010. We analyzed coexisting supraventricular tachycardias (SVT) and left atrium and PV morphology by multi-detector row CT. Thirty-eight of 137 patients (27.7 %) were found to have some PV anomaly, consisting of 13 with a common trunk of left PV, 19 with right additional PV, 3 with a common trunk of right PV, 3 with CIPV. Thirty-one patients (22.6 %) had SVT. They were: 26 atrial flutter, 4 WPW syndrome, 3 atrioventricular nodal reentrant tachycardia. The prevalence of a coexisting ACP was significantly higher in patients with CIPV than those without CIPV (3/3 (100 %) vs. 1/134 (0.7%); p<0.0001). All ACPs with CIPV were located in the left side. The other SVTs were not associated with any PV anomalies. Conclusions: -There is a possible association between CIPV and left-sided ACP in AF patients. This suggests that there is a likelihood of developmental association between them.

Circ Arrhythm Electrophysiol: 24 Mar 2011; epub ahead of print
Ihara K, Nitta J, Sato A, Iwai S, ... Hirao K, Isobe M
Circ Arrhythm Electrophysiol: 24 Mar 2011; epub ahead of print | PMID: 21430126
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Abstract

Isoproterenol Administration During General Anesthesia for the Evaluation of Children with Ventricular Preexcitation.

Moore JP, Kannankeril PJ, Fish FA
Background: -Rapid anterograde conduction in the setting of ventricular preexcitation is associated with an increased risk of sudden cardiac death. The effect of isoproterenol in this setting is unclear, particularly in younger, anesthetized patients. The aim of this study was to determine the effect of isoproterenol on accessory pathway conduction in children undergoing general anesthesia and its role in the risk stratification process. Methods and results: -The records of 151 pediatric patients with preexcitation undergoing electrophysiologic study under propofol anesthesia over a 5 year period were reviewed. Data included accessory pathway effective refractory period (APERP), minimum 1:1 accessory pathway conduction with atrial pacing (1:1 conduction), and shortest preexcited R-R interval in atrial fibrillation (SPRRI). Measurements were repeated on low-dose isoproterenol (mean 0.013 µ/kg/min, range 0.003 - 0.027). All accessory pathway characteristics shortened significantly with isoproterenol (p<0.001). APERP increased modestly with age both in the baseline state (r=0.172, p=0.04) and with isoproterenol (r=0.267, p<0.01) as did 1:1 conduction (r=0.178, p=0.034 and r=0.175, p<0.01, respectively). APERP ≤ 250 ms was observed in only 5% of patients at baseline vs 25% after isoporoterenol and SPRRI ≤ 250 ms in 16% vs 41%. Tachycardia was induced in 48/151 patients before and 102/151 after isoproterenol. Conclusions: -In anesthetized children with ventricular preexcitation, accessory pathways display shorter conduction properties at younger ages and important adrenergic sensitivity at all ages. Use of low-dose isoproterenol resulted in a substantial increase in the number of patients who would otherwise meet typical criteria for ablation.

Circ Arrhythm Electrophysiol: 15 Dec 2010; epub ahead of print
Moore JP, Kannankeril PJ, Fish FA
Circ Arrhythm Electrophysiol: 15 Dec 2010; epub ahead of print | PMID: 21156771
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Abstract

Altered Desmosomal Proteins in Granulomatous Myocarditis and Potential Pathogenic: Links to Arrhythmogenic Right Ventricular Cardiomyopathy.

Asimaki A, Tandri H, Duffy ER, Winterfield JR, ... Calkins H, Saffitz JE
Background: -Immunoreactive signal for the desmosomal protein plakoglobin (γ-catenin) is reduced at cardiac intercalated disks in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC), a highly arrhythmogenic condition caused by mutations in genes encoding desmosomal proteins. Previously, we observed a "false positive" case in which plakoglobin signal was reduced in a patient initially thought to have ARVC but who actually had cardiac sarcoidosis. Sarcoidosis can masquerade clinically as ARVC, but has not previously been associated with altered desmosomal proteins. Methods and results: -We observed marked reduction in immunoreactive signal for plakoglobin at cardiac myocyte junctions in patients with sarcoidosis and giant cell myocarditis, both highly arrhythmogenic forms of myocarditis associated with granulomatous inflammation. In contrast, plakoglobin signal was not depressed in lymphocytic (non-granulomatous) myocarditis. To determine whether cytokines might promote dislocation of plakoglobin from desmosomes, we incubated cultures of neonatal rat ventricular myocytes with selected inflammatory mediators. Brief exposure to low concentrations of IL-17, TNFα and IL-6, cytokines implicated in granulomatous myocarditis, caused translocation of plakoglobin from cell-cell junctions to intracellular sites, whereas other potent cytokines implicated in non-granulomatous myocarditis had no effect, even at much high concentrations. We also observed myocardial expression of IL-17 and TNFα, and elevated serum levels of inflammatory mediators including IL-6R, IL-8, MCP1 and MIP1β in ARVC patients (all p<0.0001 compared with controls). Conclusions: -These results suggest novel disease mechanisms involving desmosomal proteins in granulomatous myocarditis and implicate cytokines, perhaps derived in part from the myocardium, in disruption of desmosomal proteins and arrhythmogenesis in ARVC.

Circ Arrhythm Electrophysiol: 23 Aug 2011; epub ahead of print
Asimaki A, Tandri H, Duffy ER, Winterfield JR, ... Calkins H, Saffitz JE
Circ Arrhythm Electrophysiol: 23 Aug 2011; epub ahead of print | PMID: 21859801
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Abstract

Primary Prevention of Sudden Cardiac Death in Silent Cardiac Sarcoidosis: Role of Programmed Ventricular Stimulation.

Mehta D, Mori N, Goldbarg S, Lubitz S, Wisnivesky JP, Tierstein A
Background: -Cardiac involvement in sarcoidosis is often silent and may lead to sudden death. This study was designed to assess the value of programmed electrical stimulation of the ventricle (PES) for risk stratification in patients with sarcoidosis and evidence of preclinical cardiac involvement on imaging studies. Methods and results: -Patients with biopsy proven systemic sarcoidosis but without cardiac symptoms who had evidence of cardiac sarcoidosis on positron emission tomography (PET) or cardiac magnetic resonance imaging (CMR) were included. All patients underwent baseline evaluation, echocardiographic assessment of left ventricular function, and programmed electrical stimulation of the ventricle. Patients were followed for survival and arrhythmic events. Seventy-six patients underwent PES of the ventricle. Eight (11%) were inducible for sustained ventricular arrhythmias and received an implantable defibrillator. None of the noninducible patients received a defibrillator. Left ventricular ejection fraction was lower in patients with inducible ventricular arrhythmia (36.4±4.2% vs 55.8±1.5%, p<0.05). Over a median follow-up of 5 years, 6 of 8 patients in the group with inducible ventricular arrhythmias had ventricular arrhythmia or died, compared with one death in the negative group (P<0.0001). Conclusions: -In patients with biopsy-proven sarcoidosis and evidence of cardiac involvement on PET or CMR alone, positive PES may help to identify patients at risk for ventricular arrhythmia. More importantly, patients in this cohort with a negative PES appear to have a benign course within the first several years following diagnosis. PES may help to guide the use of implantable cardioverter defibrillators in this population.

Circ Arrhythm Electrophysiol: 03 Jan 2011; epub ahead of print
Mehta D, Mori N, Goldbarg S, Lubitz S, Wisnivesky JP, Tierstein A
Circ Arrhythm Electrophysiol: 03 Jan 2011; epub ahead of print | PMID: 21193539
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Abstract

TGF-β1 Mediated Fibrosis and Ion Channel Remodeling Are Key Mechanisms Producing the Sinus Node Dysfunction Associated with SCN5A Deficiency and Aging.

Hao X, Zhang Y, Zhang X, Nirmalan M, ... Huang CL, Lei M
Background: -Mutations in the cardiac Na(+) channel gene (SCN5A) can adversely affect electrical function in the heart but effects can be age-dependent. We explored for interacting effects of Scn5a-disruption and aging on the pathogenesis of sinus node dysfunction (SND) in a heterozygous Scn5a knockout (Scn5a(+/-)) mouse model. Methods and results: -We compared functional, histological and molecular features in young (3-4 month) and old (1 year) wild type and Scn5a(+/-;) mice. Both Scn5a-disruption and aging were associated with decreased heart rate variability, reduced sinoatrial node (SAN) automaticity and slowed sinoatrial conduction. They also led to increased collagen and fibroblast levels and up-regulated TGF-β1 and vimentin transcripts providing measures of fibrosis, and reduced Nav1.5 expression. All these effects were most noticeable in old Scn5a(+/-) mice. Na(+) channel inhibition by E3-Nav1.5 antibody directly increased TGF-β1 production in both cultured human cardiac myocytes and fibroblasts. Finally, aging was associated with down-regulation of a wide range of ion channel and related transcripts, again greatest in old Scn5a(+/-) mice. The quantitative results from these studies permitted computer simulations that successfully replicated the observed SAN phenotypes shown by the different experimental groups. Conclusions: -These results implicate a tissue degeneration, triggered by Nav1.5-deficiency, manifesting as a TGF-β1 mediated fibrosis accompanied by electrical remodelling, in the SND associated with Scn5a-disruption or aging. The latter effects interact to produce the most severe phenotype in old Scn5a(+/-) mice. In demonstrating this, our findings suggest a novel regulatory role for Nav1.5 in cellular biological processes additional to its electrical function.

Circ Arrhythm Electrophysiol: 15 Apr 2011; epub ahead of print
Hao X, Zhang Y, Zhang X, Nirmalan M, ... Huang CL, Lei M
Circ Arrhythm Electrophysiol: 15 Apr 2011; epub ahead of print | PMID: 21493874
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This program is still in alpha version.