Heart Rhythm - Articles in Press

Ablation of Ventricular Arrhythmias Arising Near the Anterior Epicardial Veins from the Left Sinus of Valsalva Region: ECG Features, Anatomic Distance And Outcome - Accepted Manuscript

2012-02-03

Abstract: Background: Left ventricular outflow tract tachycardia/premature depolarizations (VT/VPDs) arising near the anterior epicardial veins may be difficult to eliminate through the coronary venous system. Objective: To describe the characteristics of an alternative successful ablation strategy targeting the left sinus of Valsalva (LSV) and/or adjacent LV endocardium. Methods: Of 276 patients undergoing mapping/ablation for outflow tract VT/VPDs, 16 consecutive patients (8 men; 52±17 years) had an ablation attempt from the LSV and/or adjacent LV endocardium for VT/VPDs mapped marginally closer to the distal great cardiac vein (GCV) or anterior interventricular vein (AIV). Results: Successful ablation was achieved in 9/16 patients (56%) targeting the LSV (5 patients), adjacent LV endocardium (2 patients) or both (2 patients). R wave amplitude ratio in III/II and Q wave amplitude ratio in aVL/aVR were smaller in the successful group (1.05±0.13 versus 1.34±0.37 and 1.24±0.42 versus 2.15±1.05, respectively, P=0.043 for both). Anatomical distance from earliest GCV/AIV site to closest point in LSV region was shorter for the successful group, 11.0±6.5 mm versus 20.4±12.1 mm, P=0.048. Q wave ratio in aVL/aVR <1.45 and anatomical distance <13.5 mm had sensitivity and specificity of 89%, 75% and 78%, 64% respectively for identifying successful ablation. Conclusion: VT/VPDs originating near the GCV/AIV can be ablated from the LSV/adjacent LV endocardium. Q wave ratio aVL/aVR <1.45 and close anatomical distance <13.5 mm help identify appropriate candidates.

Epicardial Ganglionated Plexus Stimulation Decreases Post-Operative Inflammatory Response in Humans - Accepted Manuscript

2012-02-03

Abstract: Background: Surgical cardiac revascularization produces a high degree of systemic inflammation and the secretion of several cytokines. Intensive post-operative inflammation may increase the incidence of post-operative atrial fibrillation and favor organ dysfunctions. No data documenting the anti-inflammatory properties of epicardial vagal ganglionated plexus stimulation are available. Objective: The aims of the present study were to verify the feasibility and safety of post-operative inferior vena cava-inferior atrial ganglionated plexus (IVC-IAGP) burst stimulation and the effectiveness of this approach in reducing serum levels of inflammatory cytokines. Methods: In 27 patients who were candidates for off-pump surgical revascularization, the IVC-IAGP was located during surgery, a temporary wire was inserted and negative atrio-ventricular node dromotropic effect was obtained in 20 patients on applying high-frequency burst stimulation. In 5 patients AF or phrenic nerve stimulation was induced, the remaining 15 patients served as experimental group (EG). Twenty additional patients underwent off-pump surgical revascularization without IVC-IAGP stimulation and served as a control group (CG). On arrival in Intensive Care Unit, EG underwent IVC-IAGP stimulation for 6 hours. Blood samples were collected at different times. Results: The serum levels of cytokines were not statistically different at baseline and on arrival in Intensive Care Unit between the groups, while proved statistically different after 6 hours of stimulation: Interleukin-6 (EG:121±71pg/ml versus CG:280±194pg/ml; p=0.001), Tumor Necrosis Factor-ą (EG:2.68±1.81pg/ml versus CG:5.87±3.48pg/ml; p=0.001), Vascular Endothelial Growth Factor (EG:93±43pg/ml versus CG:177±86pg/ml; p=0.002) and Epidermal Growth Factor (EG:79±48pg/ml versus CG:138±76pg/ml; p=0.019). Conclusions: prolonged burst IVC-IAGP stimulation after surgical revascularization appears feasible and safe and significantly reduces inflammatory cytokines in the post-operative period.

Impairment of trafficking by downregulation of an anchor protein: novel insights into additional mechanisms responsible for heart failure - Accepted Manuscript

Marc A. Vos, Karin R. Sipido — 2012-02-02

High Degree Right Bundle Branch Block Obscuring the Diagnosis of Brugada Electrocardiographic Pattern - Accepted Manuscript

Pablo A. Chiale, Hugo A. Garro, Pablo A. Fernández, Marcelo V. Elizari — 2012-02-02

Abstract: Brugada syndrome is a disorder characterized by sudden death or potentially malignant ventricular tachyarrhythmias associated in the most typical cases with an electrocardiographic (ECG) pattern combining a coved type ST elevation (≥0, 2 mV), a negative T wave and a “pseudo” right bundle branch block (RBBB) morphology in two or more right precordial leads (1-3). In this report we demonstrate that a “true” high degree RBBB can conceal the typical ST elevation in right precordial leads that is essential for the diagnosis of Brugada syndrome.

R-on-T and Cardiac Arrest from Dual-Chamber Pacing without an Atrial Lead - Accepted Manuscript

Peter M. Schulman, Eric C. Stecker, Marc Rozner — 2012-02-01

Plasma BIN1 correlates with heart failure and predicts arrhythmia in patients with arrhythmogenic right ventricular cardiomyopathy - Accepted Manuscript

2012-02-01

Abstract: Background: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a disorder involving diseased cardiac muscle. BIN1 is a membrane associated protein important to cardiomyocyte homeostasis and is down regulated in cardiomyopathy. We hypothesized that BIN1 could be released into the circulation and that blood-available BIN1 can provide useful data on the cardiac status of patients whose hearts are failing due to ARVC. Objective: To determine whether plasma BIN1 can measure disease severity in patients with ARVC. Methods: We performed a retrospective cohort study of 24 patients with ARVC. Plasma BIN1 levels were assessed for their ability to predict cardiac functional status and ventricular arrhythmias. Results: Mean plasma BIN1 levels were decreased in ARVC patients with heart failure (15 ± 7 vs. 60 ± 17 in patients without heart failure, p<0.05; plasma BIN1 is 60±10 in non-ARVC normal controls). BIN1 levels correlated inversely with ventricular arrhythmia (R=-0.47, p<0.05), and low BIN1 correctly classified patients with advanced heart failure or ventricular arrhythmia (ROC Area under the curve, AUC, of 0.88±0.07). Low BIN1 also predicted future ventricular arrhythmias (ROC AUC of 0.89±0.09). In a stratified analysis, BIN1 could predict future arrhythmias in patients without severe heart failure (n=20) with an accuracy of 82 %. In the seven ARVC patients with serial blood samples, all of whom had evidence of disease progression during follow up, plasma BIN1 decreased significantly (decrease of 63 %, p<0.05). Conclusions: Plasma BIN1 seems to correlate with cardiac functional status and presence or absence of sustained ventricular arrhythmias in a small cohort of ARVC patients and can predict future ventricular arrhythmias.

The phenomenon of "QT-stunning": The abnormal QT prolongation provoked by standing, in patients with long QT syndrome, persists even as the heart rate returns to normal - Accepted Manuscript

2012-02-01

Abstract: Objectives: To describe a novel observation, coined "QT-stunning" and to validate previous observations regarding the "QT-stretching" phenomenon in patients with long QT syndrome (LQTS) utilizing our recently described "standing-test." Background: Patients with LQTS have inadequate shortening of the QT interval in response to the sudden heart-rate accelerations provoked by standing, a phenomenon of diagnostic value. We now validate our original observations in a cohort twice as large. We also describe that this abnormal QT-response persists as the heart rate acceleration returns to baseline. Methods: The electrocardiograms (ECG) of 108 patients with LQTS and 112 healthy subjects were recorded in the supine position. Subjects were then instructed to stand up quickly and remain standing for 5-minutes during continuous ECG recording. The QT was measured at baseline (QTcbase), when heart rate acceleration without appropriate QT shortening leads to maximal “QT stretching” (QTcstretch) and upon return of heart rate to baseline (QTcreturn). Results: QTcstretch lengthened significantly more in LQT-patients (103±80 msec vs. 66±40 msec in controls, p<0.001) and so did QTcreturn (28±48 msec for LQT-patients vs. -3±32 msec for controls, p<0.001). Using a sensitivity cutoff of 90%, the specificity for diagnosing LQTS was 74% for QTcbase, 84% for QTc return and 87% for QTcstretch. Conclusions: The present study extends our previous findings on the abnormal response of the QT interval in response to standing in patients with LQTS. Our study also shows that this abnormal response persists even after the heart rate slows back to baseline.

EP News: Basic and Translational - Uncorrected Proof

Peng-Sheng Chen — 2012-01-30

Gersh et al (Circulation 2011;13:124, PMID 22068435) updated the ACCF/AHA guideline for the diagnosis and treatment of hypertrophic cardiomyopathy (HCM). In this updated recommendation for HCM, genetic testing is listed as a Class I recommendation to evaluate patients with HCM. All patients who undergo genetic testing should also undergo genetic counseling. Genetic screening is recommended in first-degree relatives of patients with HCM. In addition, genetic testing is recommended for patients with an atypical clinical presentation of HCM or when another genetic condition is suspected to be the cause. However, the Task Force also played down the importance of using specific mutations to predict the likelihood of sudden cardiac death (SCD). While some earlier works found certain mutations are “malignant”, subsequent studies showed in some instances the rate of adverse events (and prevalence of associated SCD risk markers) was lower in patients with “malignant” mutations than it was in those with mutations believed to be “benign.” The endorsement of ACCF and AHA on genetic testing in HCM is an important milestone for the translation of genetic research results into clinical practice.

EP News: Clinical - Uncorrected Proof

N.A. Mark Estes — 2012-01-30

Thibault and colleagues (Circulation 2011; 124(25):2874–2881. PMID: 22104549) compared the effects of LV and biventricular (BiV) pacing on exercise tolerance and LV remodeling in patients with an LVEF ≤35%, QRS ≥120 msec, and heart failure in a multicenter, double-blind randomized trial. 121 patients were randomized to LV followed by BiV pacing or vice versa for consecutive 6-month periods. Exercise duration at 75% of peak Vo(2) (primary outcome) increased from 9.3 ± 6.4 to 14.0 ± 11.9 and 14.3 ± 12.5 minutes with LV and BiV pacing, respectively (P = 0.4). LV ejection fraction improved from 24.4 ± 6.3% to 31.9 ± 10.8% and 30.9 ± 9.8% with LV and BiV pacing, respectively (P = 0.5). Reductions in LV end-systolic volume were similar (P = 0.6788). The proportion of clinical responders (≥ 20% increase in exercise duration) to LV and BiV pacing was 48.0% and 55.1% (P = 0.2). Positive remodeling was observed in 46.7% and 55.4% (P = 0.09). Overall, 30.6% of LV nonresponders improved with BiV and 17.1% of BiV nonresponders improved with LV pacing. The authors conclude that LV pacing is not superior to BiV pacing but nonresponders to BiV pacing may respond favorably to LV pacing.

Radiation Exposure: A Silent Complication of Catheter Ablation Procedures - Accepted Manuscript

Mahmoud Houmsse, Emile G. Daoud — 2012-01-30

Disease modification by autonomic nerve stimulation - Accepted Manuscript

Seil Oh — 2012-01-30

Can Fragmented QRS help in Risk Stratifying Patients with Coronary Artery Disease and a Relatively Preserved Ejection Fraction? - Accepted Manuscript

Mithilesh Kumar Das — 2012-01-30

Electrophysiologic Characteristics and Catheter Ablation of Ventricular Tachyarrhythmias Among Heart Failure Patients on Ventricular Assist Device Support - Accepted Manuscript

2012-01-30

Abstract: Background: Ventricular tachyarrhythmias (VT) are common among ventricular assist device (VAD) recipients, yet electrophysiologic (EP) characteristics and catheter ablation outcomes remain uncharacterized. Objective: To evaluate the EP characteristics and catheter ablation outcomes for ventricular tachyarrhythmias among heart failure patients on VAD support. Methods: Cleveland Clinic registry of consecutive VAD recipients 1991-2010 with medically refractory, symptomatic VT referred for EP study and catheter ablation. Results: Among 611 VAD recipients (age 53.5 ± 12.4 yrs, 80% male), 21 pts (3.4%) were referred for 32 EP procedures including 11 pts (52%) presenting with ICD therapy (13 shocks, 26 ATP). Data from 44 inducible tachycardias (mean CL 339 ± 59 ms) demonstrated monomorphic VT (n = 40, 91%; superior axis 52%, RBBB morphology 41%) and PMVT/VF (n=4, 8%). Electroanatomic mapping of 28 tachycardias in 20 pts demonstrated re-entrant VT related to intrinsic scar (n=21/28, 75%) more commonly than the apical inflow cannulation site (n=4/28, 14%), focal/micro re-entry VT (n=2/28, 7%) or bundle-branch re-entry (n=1/28, 3.5%). Catheter ablation succeeded in 18 / 21 pts (86%). VT recurred in 7/21 pts (33%) at mean 133 ± 98 days and 6 pts (29%) required repeat procedures with subsequent recurrence in 4 / 21 pts (19%). Conclusion: Catheter ablation of VT is effective among VAD recipients. Intrinsic myocardial scar, rather than the apical device cannulation site, appears to be the dominant substrate.

The Durability of Pulmonary Vein Isolation Using the Visually-Guided Laser Balloon Catheter: Multicenter Results of Pulmonary Vein Remapping Studies - Accepted Manuscript

2012-01-30

Abstract: Objective: We sought to determine the durability of pulmonary vein (PV) isolation following ablation using the balloon-based visually-guided laser ablation (VGLA) catheter. Background: The VGLA catheter is a compliant, variable diameter balloon that delivers laser energy around the PV ostium under real-time endoscopic visualization. While acute PV isolation has been shown to be feasible, there is limited data regarding durability of isolation. Methods: The VGLA catheter was evaluated in paroxysmal atrial fibrillation (AF) patients (3 sites, 10 operators). Following transseptal puncture, the VGLA catheter was advanced through a 12-Fr deflectable sheath and inflated at the target PV ostium. Under endoscopic guidance, the 30° aiming arc was maneuvered around the PV and laser energy delivered to ablate tissue in a contiguous/overlapping manner. At ~3 months, all patients returned for a PV remapping procedure. Results: In 56 patients, 202/206 (98%) PVs were acutely isolated. At 105±44 (mean±sd) days, 52 patients returned for PV remapping at which time 162/189 PVs (86%) remained isolated and 32/52 patients (62%) had all PVs still isolated. Comparing operators performing <10 vs. ≥10 procedures, the durable PVI rate and percentage of patients with all PVs isolated were 73% vs. 89% (p = 0.011), and 57% vs. 66% (p = 0.746), respectively. After two procedures and 12.0±1.9 months of follow-up, the drug-free rate of freedom from AF was 71.2%. Conclusions: In this multicenter, multi-operator experience, VGLA resulted in a very high rate of durable PV isolation with a clinical efficacy similar to radiofrequency ablation.

Combined Assessment of Gender and Mutation-Specific Information for Risk Stratification in Type 1 Long QT Syndrome - Accepted Manuscript

2012-01-30

Abstract: Background: Men and women with type-1 long QT syndrome (LQT1) exhibit time-dependent differences in the risk for cardiac events. Objectives: We hypothesized that gender-specific risk in LQT1 is related to the location and function of the disease-causing mutation in the KCNQ1gene. Methods: The risk for life-threatening cardiac events (comprising aborted cardiac arrest [ACA] or sudden cardiac death [SCD]) from birth through age 40 years was assessed among 1,051 individuals with LQT1, 450 males/601 females, by the location and function of the LQT1-causing mutation (pre-specified as mutations in the intracellular domains linking the membrane spanning segments [i.e. S2-S3 and S4-S5 cytoplasmic [C]-loops] involved in adrenergic channel regulation vs. other mutations). Results: Multivariate analysis showed that during childhood (age-group: 0-13 years) males had >2-fold (p<0.003) increased risk for ACA/SCD compared with females, whereas after the onset of adolescence the risk for ACA/SCD was similar between males and females (HR=0.89 [p=0.64]). The presence of C-loops mutations was associated with a 2.7-fold (p<0.001) increased risk for ACA/SCD among females, but did not affect risk among males (HR=1.37; p=0.26). Time-dependent syncope was associated with a more pronounced risk-increase among males than among females (HR = 4.73 [p<0.001] and 2.43 [p=0.02], respectively), whereas a prolonged QTc (≥500 msec) was associated with a higher risk among females than in males. Conclusion: Our findings suggest that combined assessment of clinical and mutation location/functional data can be used to identify gender-specific risk factors for life-threatening events for patients with type-1 long QT syndrome.

Post Repolarization Refractoriness in Acute Ischemia and after Antiarrhythmic Drug Administration: Action Potential Duration is not Always an Index of the Refractory Period - Accepted Manuscript

R. Coronel, M.J. Janse, T. Opthof, A.A. Wilde, P. Taggart — 2012-01-30

Abstract: Background: Action potential duration is widely used as a measure of refractory period in ischemia. Whereas the end of repolarization closely corresponds to the end of refractoriness in well perfused, well oxygenated myocardium, it is no longer true for ischemic myocardium where recovery of excitability lags behind full repolarization. Objective: The purpose of this paper is to review this phenomenon of post-repolarization-refractoriness during ischemia and after application of various antiarrhythmic drugs. Conclusion: Whereas post repolarization refractoriness is profoundly pro-arrhythmic during ischemia, it may protect the heart from re-entrant arrhythmias in the absence of depolarization of the resting membrane. Increase of post repolarization refractoriness induced by sodium channel blocking drugs may exert an antifibrillatory action.

Sex Hormones and Ventricular Tachyarrhythmias in LQTS: New Insights Regarding Antiarrhythmic Therapy - Accepted Manuscript

Arthur J. Moss — 2012-01-20

The Riata Story—Where are we now? - Accepted Manuscript

Charles A. Henrikson — 2012-01-16

Drug-induced QT-interval shortening following antiepileptic treatment with oral rufinamide - Uncorrected Proof

2012-01-13

Background: The arrhythmogenic potential of short QT intervals has recently been highlighted in patients with a short QT syndrome. Drug-induced QT-interval prolongation is a known risk factor for ventricular tachyarrhythmias. However, reports on drug-induced QT-interval shortening are rare and proarrhythmic effects remain unclear. Objective: Recently, rufinamide, a new antiepileptic drug for the add-on treatment of Lennox-Gastaut syndrome, was approved in the European Union and the United States. Initial trials showed drug-induced QT-interval shortening. The aim of our study was to evaluate the effects of rufinamide on QT intervals in patients with difficult-to-treat epilepsies. Methods: Nineteen consecutive patients with Lennox-Gastaut syndrome and other epilepsy syndromes were included (n = 12 men; mean age 41 ± 12 years). QRS, QT, and Tpeak-Tend intervals were analyzed before and during rufinamide treatment. Results: The mean QT interval shortened significantly following rufinamide administration (QT interval 349 ± 23 ms vs 327 ± 17 ms; corrected QT interval 402 ± 22 ms vs 382 ± 16 ms; P = .002). Tpeak-Tend intervals were 79 ± 17 ms before and 70 ± 20 ms on treatment (P = .07). The mean reduction in the corrected QT interval was 20 ± 18 ms. During follow-up (3.04 ± 1.09 years), no adverse events including symptomatic cardiac arrhythmias or sudden cardiac deaths were observed. Conclusion: QTc-interval shortening following oral rufinamide administration in a small patient group was not associated with significant clinical adverse effects. These observations nothwithstanding, the ability of rufinamide to significantly shorten the QT interval portends a potential arrhythmogenic risk that may best be guarded against by periodic electrocardiographic recordings.

Subclinical left ventricular dysfunction revealed by circumferential 2D strain imaging in patients with coronary artery disease and fragmented QRS complex - Uncorrected Proof

2012-01-13

Background: Fragmented QRS (fQRS) complexes on a routine 12-lead electrocardiogram were associated with adverse cardiac events, including sudden death in patients with coronary artery disease (CAD). Objective: To investigate the relationship between the fQRS complex and global and regional left ventricular (LV) functions in patients with CAD. Methods: The study consisted of 176 patients (68 ± 9 years; 145 [82%] men) with CAD with narrow QRS duration and preserved LV ejection fraction (>45%). All patients underwent detailed 2-dimensional speckle-tracking echocardiography to determine global and segmental (basal, middle, and apical) LV strains and strain rates and were prospectively followed-up in the outpatient clinic. Results: Fifty-five patients (31%) had fQRS complexes. Global, middle, and apical LV longitudinal, radial, and circumferential strains and strain rates were significantly lower in the fQRS group than in the non-fQRS group (all P <.05). Multivariate logistic regression analysis revealed that the fQRS complex was associated with decreased global circumferential strain (odds ratio 1.19; 95% confidence interval 1.06−1.33; P = .003) and multivessel disease (odds ratio 3.69; 95% confidence interval 1.35−10.08; P = .011). Kaplan-Meier analysis revealed that event-free survival for cardiac events was significantly lower in the fQRS group than in the non-fQRS group (P = .036). Conclusions: Our results demonstrated that the fQRS complex in patients with CAD with preserved LV ejection fraction was associated with subclinical global and regional LV dysfunctions as detected by 2-dimensional speckle-tracking imaging, and the results also predicted adverse cardiac events.

Atrial fibrillation substrate: The “unknown species”— From lone atrial fibrillation to fibrotic atrial cardiomyopathy - Uncorrected Proof

Hans Kottkamp — 2012-01-13

Catheter ablation of atrial fibrillation (AF) is now a routine procedure with pulmonary vein (PV) isolation as the cornerstone. However, the consequences of ablation on the structural atrial remodeling process of the underlying chronic and progressive disease are widely unknown.

Estradiol promotes sudden cardiac death in transgenic long QT type 2 rabbits while progesterone is protective - Uncorrected Proof

2012-01-13

Background: Postpubertal women with inherited long QT syndrome type 2 (LQT2) are at increased risk for polymorphic ventricular tachycardia (pVT) and sudden cardiac death (SCD), particularly during the postpartum period. Objective: To investigate whether sex hormones directly modulate the arrhythmogenic risk in LQTS. Methods: Prepubertal ovariectomized transgenic LQT2 rabbits were treated with estradiol (EST), progesterone (PROG), dihydrotestosterone (DHT), or placebo (OVX). Results: During 8 weeks of treatment, major cardiac events—spontaneous pVT or SCD—occurred in 5 of the 7 EST rabbits and in 2 of the 9 OVX rabbits (P <.05); in contrast, no events occurred in 9 PROG rabbits and 6 DHT rabbits (P <.01 vs PROG; P <.05 vs DHT). Moreover, EST increased the incidence of pVT (P <.05 vs OVX), while PROG reduced premature ventricular contractions, bigeminy, couplets, triplets, and pVT (P <.01 vs OVX; P <.001 vs EST). In vivo electrocardiographic monitoring, in vivo electrophysiological studies, and ex vivo optical mapping studies revealed that EST promoted SCD by steepening the QT/RR slope (P <.05), by prolonging cardiac refractoriness (P <.05), and by altering the spatial pattern of action potential duration dispersion. Isoproterenol-induced Ca2+ oscillations resulted in early afterdepolarizations in EST-treated hearts (4 of 4), while PROG prevented SCD by eliminating this early afterdepolarization formation in 4 of the 7 hearts (P = .058 vs EST; P <.05 vs OVX). Analyses of ion currents demonstrated that EST increased the density of ICa,L as compared with OVX (P <.05) while PROG decreased it (P <.05). Conclusion: This study reveals the proarrhythmic effect of EST and the antiarrhythmic effect of PROG in LQT2 in vivo, outlining a new potential antiarrhythmic therapy for LQTS.

Ranolazine stabilizes cardiac Ryanodine receptors: a novel mechanism for the suppression of Early afterdepolarization and Torsade de Pointes in Long QT type 2 - Accepted Manuscript

2012-01-13

Abstract: Background: Ranolazine (Ran) is known to inhibit multiple targets, including: the late Na+ current, INa, the rapid delayed rectifying K+ current IKr, L-type Ca2+ current ICa,L, and fatty-acid metabolism. Functionally, Ran suppresses early afterdepolarization (EADs) and Torsade de Pointes (TdP) in drug-induced long QT type 2 (LQT2) presumably by decreasing intracellular [Na+]i and Ca2+ overload. However, simulations of EADs in LQT2 failed to predict their suppression by Ran. Objectives: To elucidate the mechanism(s) whereby Ran alters cardiac action potentials (APs) and cytosolic Ca2+ transients (CaiT) and suppresses EADs and (TdP) in LQT2. Methods: The known effects of Ran were inserted in simulations (Shannon and Mahajan models) of rabbit ventricular APs and CaiT in control and LQT2 models and compared to experimental optical mapping data from Langendorff rabbit hearts treated with E4031 (0.5 M) to block IKr. Direct effects of Ran on cardiac ryanodine receptors (RyR2) were investigated in single channels and changes in Ca2+-dependent high-affinity ryanodine binding. Results: Ran (10μM) alone prolonged APDs (206±4.6 to 240±7.8 ms; p< 0.05); E4031 prolonged APDs (204±6 to 546±35 ms) and elicited EADs and TdP that were suppressed by Ran (10μM, n=7/7 hearts). Simulations (Shannon but not Mahajan model) closely reproduced experimental data except for EAD-suppression by Ran. Ran reduced Po of RyR2 (IC50=10±3μM; n=7) in bilayers and shifted EC50 for Ca2+-dependent ryanodine-binding from 0.42±0.02 to 0.64±0.02 M with 30 M Ran. Conclusions: Ran reduces Po of RyR2, desensitizes Ca2+-dependent RyR2 activation and inhibits Cai oscillations which represents a novel mechanism for its suppression of EADs and TdP.

Letter to the Editor - Advice for “Proud Flesh” Post Permanent Pacemaker - Accepted Manuscript

Victor Parsonnet — 2012-01-13

Advice for "Proud Flesh" Post Permanent Pacemaker article Author reply - Accepted Manuscript

Siddharth A. Kakodkar, Richard G. Trohman — 2012-01-13

“J-wave syndromes” bring the ATP-sensitive potassium channel back in the spotlight - Uncorrected Proof

Arthur A.M. Wilde — 2012-01-05

Early repolarization syndrome (ERS) is the newest “kid on the block” of the so-called electrical cardiomyopathies. Its electrocardiographic signature, together with its association with malignant arrhythmias first described by Haissaguerre et al, is a popular disease entity in recent years. This concerns the prognostic significance, in particular of relevance given its high prevalence in subsets of the population, its pathophysiological substrate, and its genetic basis. The last two are the subject of this commentary.

Expecting the unpredictable - Uncorrected Proof

Beat Schaer, Christian Sticherling — 2012-01-05

Dr Schaer received research grants from Boston Scientific and St Jude Medical and has a speakers' bureau appointment with Medtronic. Dr Sticherling received research grants from Biotronik and Boston Scientific and has a speakers' bureau appointment with Medtronic, Biotronik, Boston Scientific, and Sorin.

Average T-wave alternans activity in ambulatory electrocardiogram records: Commentary on the relationship with T-wave amplitude and T-wave alternans regionality - Uncorrected Proof

2012-01-04

We thank Dr Madias for his kind comments and the interest in our paper, and we would like to comment on the points raised. Dr Madias' first question was about the relationship between T-wave alternans (TWA) and the amplitude of the JT segment. We agree that when studying local TWA amplitudes, the question of whether TWA depends on the T-wave amplitude could be of interest, as it might indicate that adjusting local TWA values to T-wave amplitudes could improve the value of TWA clinical indices. With the approach proposed in our work, however, the effect of T-wave amplitudes on TWA indices is no longer a one-to-one relationship. The indices proposed in our paper depend not only on local TWA amplitudes but also on the percentage of time with TWA in a 24-hour period. This means, for example, that the index of average alternans would be low for electrocardiograms presenting high-amplitude TWA during a small percentage of time. This particular framework, therefore, is not appropriate to determine the exact influence of JT amplitudes on TWA indices.

Interactions between atrial electrical remodeling and autonomic remodeling: How to break the vicious cycle - Uncorrected Proof

2012-01-04

Background: The mechanism(s) underlying the maintenance of atrial fibrillation (AF) during the first few hours after AF was initiated remains poorly understood. Objective: To investigate the roles of the intrinsic cardiac autonomic nervous system in the maintenance of AF at the early stage. Methods: In 10 anesthetized dogs, we attached multielectrode catheters on atria and pulmonary veins. Microelectrodes inserted into the anterior right ganglionated plexi recorded neural activity. At baseline, programmed stimulation determined the effective refractory period (ERP) and window of vulnerability (WOV), a measure of AF inducibility. For the next 6 hours, AF was simulated by rapid atrial pacing (RAP) and the same parameters were measured hourly during sinus rhythm. A circular catheter was positioned in the superior vena cava for high-frequency stimulation (20 Hz) of the adjacent vagal preganglionics. During 4−6 hours of RAP, we delivered low-level vagal stimulation in the superior vena cava (LL-SVCS), 50% below that which induced slowing of the sinus rate. Results: During 6-hour RAP, there was a progressive decrease in the ERP and an increase in ERP dispersion, WOV, and neural activity. With LL-SVCS during 4−6-hour RAP, ERP, WOV, and neural activity returned toward baseline levels (all P <.05, compared with the third-hour RAP values). Conclusions: RAP not only induces atrial electrical remodeling but also promotes autonomic remodeling. These 2 remodeling processes may form a vicious cycle and each may perpetuate the other. These findings may help to explain how AF maintains itself in its very early stage. LL-SVCS both reversed remodeling processes and can potentially break the vicious cycle of “AF begets AF” in the first few hours of AF.

Predictors of long-term success after catheter ablation of atriofascicular accessory pathways - Uncorrected Proof

2012-01-04

Background: Electrophysiologic characteristics, mapping strategies, and acute success rates of radiofrequency catheter ablation of atriofascicular accessory pathways are well described. However, data on long-term prognosis and predictors for freedom from arrhythmias are lacking. Objective: To report our 20-year single-center experience on ablation of atriofascicular fibers. Method: Between 1992 and 2010, 34 patients with atriofascicular accessory pathways underwent catheter ablation at our institution because of symptomatic antidromic atrioventricular reentrant tachycardias. Radiofrequency procedures were retrospectively analyzed, and patients were followed for recurrences of tachyarrhythmias. Electrocardiograms (before and after ablation and at follow-up) were analyzed for each patient. Results: Successful catheter ablation of the atriofascicular fiber was achieved in 23 (68%) patients. Mechanical block during mapping occurred in 3 (9%) patients, and in 2 of them ablation was performed at the site of mechanical block. Mere modification of conduction properties of the pathway without complete block was achieved in 5 patients (15%). Fast pathway ablation was performed in 2 (6%) of the patients ablated in the early 1990s. During follow-up of 9.3 ± 5.5 years, 24 patients (71%) remained free of tachyarrhythmias, 7 reported significant improvement, and 3 (9%) had no change in symptoms after ablation. Long-term success was identical between patients from the first (1992–1999) and second (2000–2010) decade (12 of 17 [71%] vs 12 of 17 [71%]). It was 87% in those with complete block of the atriofascicular fiber while all patients with mechanical block during mapping reported recurrences. Fast pathway ablation was complicated by complete atrioventricular block in 1 patient, who required pacemaker implantation 18 years after ablation owing to loss of conduction properties of the atriofascicular fiber over the years. On analyzing patients with preexcitation before ablation (n = 16; 47%), we found that the PR interval after ablation was significantly longer only in those without recurrence (162 ± 21 ms vs 134 ± 21 ms; P = .042). None of the other analyzed electrocardiographic parameters, including PR, QRS duration, and preexcitation, had prognostic impact. Conclusion: Acute success of complete ablation of atriofascicular pathways is associated with excellent long-term success (87%). Mere modification of conduction properties of atriofascicular fibers or ablation at the sites of mechanical block are less promising end points of ablation with high recurrence rates. Technical innovations during decades may not further improve long-term outcome in these patients.

Contact force–controlled zero-fluoroscopy catheter ablation of right-sided and left atrial arrhythmia substrates - Uncorrected Proof

2012-01-04

Background: Conventional catheter ablation of cardiac arrhythmias is associated with radiation risks for patients and laboratory personnel. However, nonfluoroscopic catheter guidance may increase the risk for inadvertent cardiac injury. A novel radiofrequency ablation catheter capable of real-time tissue-tip contact force measurements may compensate for nonfluoroscopic safety issues. Objective: To investigate the feasibility of contact force–controlled zero-fluoroscopy catheter ablation. Methods: In 30 patients (including 12 pediatric patients), zero-fluoroscopy catheter ablation of right-sided (right atrium, n = 20; right ventricle, n = 2) and left atrial (n = 8) arrhythmias was attempted. Inclusion criteria were symptomatic suspected atrioventricular nodal reentrant tachycardia, atrioventricular reentrant tachycardia, focal right atrial and ventricular arrhythmias, and lone atrial fibrillation. A novel irrigated-tip catheter with an integrated contact force sensor was used for nonfluoroscopic 3-dimensional electroanatomical mapping and radiofrequency ablation. Transseptal access was gained under transesophageal guidance for ablation of left-sided arrhythmias. Results: Procedural success without fluoroscopy was achieved in 29 of the 30 patients (97%). In 1 patient, endocardial nonfluoroscopic ablation failed because of an epicardial accessory pathway within a coronary sinus aneurysm. Mean total contact force and amplitude of force undulations were kept below 50 g during mapping and below 40 g during ablation to prevent contact force peaks (>100 g). Apart from a transient second-degree type I atrioventricular block, no complications occurred. The mean procedure time was 2.8 ± 0.9 hours. There were no arrhythmia recurrences during a mean follow-up of 6.2 ± 4.2 months. Conclusion: Contact force–controlled zero-fluoroscopy catheter ablation is generally feasible in right-sided and left atrial cardiac arrhythmias.

Reaching the ventricular aspect of the inferior isthmus in a Fontan patient using magnetic navigation - Uncorrected Proof

Akiko Ueda, Irina Horduna, Michael Rubens, Sabine Ernst — 2012-01-04

After classic Fontan operation, that is, atriopulmonary connection, up to 50% of the patients develop atrial tachycardia (AT) during long-term follow-up. The majority of atrial arrhythmias following the Fontan procedure are ATs related to surgical incision or inferior isthmus-dependent flutter.

Continuous ECGI mapping of spontaneous VT initiation, continuation, and termination with antitachycardia pacing - Uncorrected Proof

2012-01-04

A 40-year-old woman with nonischemic cardiomyopathy and a left ventricular (LV) ejection fraction of 35% was referred for recurrent ventricular tachycardia (VT). She experienced 248 VT episodes treated by antitachycardia pacing (ATP) over 14 days. In 2005, she received an implantable cardioverter-defibrillator for an episode of syncope and nonsustained VT. She later underwent an invasive electrophysiology study (EPS) with inducible VT and an ablation of the AV nodal reentrant tachycardia. Since then, she experienced symptomatic VT, terminated by ATP. Her VT was unresponsive to sotalol and mexiletine. Two EPS in early 2010 failed to induce VT despite intravenous isoproterenol and triple extrastimuli at 2 right ventricular (RV) sites; therefore, no ablations were performed.

Abrupt bradycardia and grouped beating during treadmill testing: A mimic of upper rate behavior - Uncorrected Proof

Christopher E. Woods, Karen Friday, Paul Wang, Mintu P. Turakhia — 2012-01-03

We describe a case of an abrupt-onset grouped beating and a decline in the paced ventricular rate during treadmill testing. The differential diagnosis is presented, and a systematic evaluation confirms that a mimic of upper rate behavior is the cause. We demonstrate that wireless interrogation performed during stress testing can be a useful method for device troubleshooting.

SCN1Bb, atrial fibrillation, and Brugada syndrome: Just another brick in the wall … - Uncorrected Proof

Vincent Probst, Jean-Baptiste Gourraud, Hervé Le Marec — 2012-01-03

“Brugada syndrome (BrS) is an inherited cardiac arrhythmia characterized by an ST segment elevation in the right precordial leads and an associated risk of sudden cardiac death due to ventricular fibrillation.”

Electrocardiographic characteristics of patients with false tendon: Possible association of false tendon with J waves - Uncorrected Proof

2012-01-03

Background: The false tendons (FTs) are fibromuscular bands that transverse the left ventricular cavity and often contain conduction tissue, suggesting that FTs may contribute to the occurrence of ventricular arrhythmias. The presence of J waves is associated with vulnerability to ventricular arrhythmias; however, the mechanisms underlying the manifestation of J waves remain to be elucidated. Objective: To investigate the electrocardiographic characteristics, including the presence of J waves, in patients with FTs. Methods: We studied 44 patients with distinct FTs detected by echocardiography (FT group) and 88 age- and sex-matched healthy subjects without FTs (control group). The PQ, QRS, JT, QT, corrected JT, and corrected QT intervals were automatically measured on surface 12-lead electrocardiograms, and the presence or absence of J waves was also determined. J waves were defined as terminal QRS notching or slurring. FTs were classified according to their points of attachment as type 1 (longitudinal, 52%), type 2 (diagonal, 25%), type 3 (transverse, 16%), and type 4 (weblike, 7%). Results: QRS and corrected QT intervals were significantly longer in the FT group than in the control group (P <.005 and P <.05, respectively). The incidence of J waves was significantly higher in the FT group (64%) than in the control group (19%) (P <.0001). J waves were more prevalent in type 1 (78%) and type 2 (73%) than in type 3 (14%) and 4 FTs (33%) (P <0.05) and in patients with thick FTs (≥2 mm) than with thinner FTs (<2 mm) (71% vs 33%; P <.05). The J-wave location differed according to the FT type. Conclusions: Our results suggest that FTs may carry a certain role to the genesis of J waves.

Riata implantable cardioverter-defibrillator lead failure: Analysis of explanted leads with a unique insulation defect - Uncorrected Proof

Robert G. Hauser, Deepa McGriff, Linda Kallinen Retel — 2011-12-30

Background: The Riata family of implantable cardioverter-defibrillator leads (St Jude Medical, Sylmar, CA) appears prone to a unique failure mechanism whereby the conductor cables wear through the silicone insulation from inside-out and are seen outside the lead body (externalized conductors). Objective: To assess the extent of Riata lead damage associated with inside-out insulation defects and their clinical consequences. Methods: In September 2011, we searched the U.S. Food and Drug Administration's Manufacturers and User Defined Experience medical device database for reports describing Riata lead failures that had been analyzed by the manufacturer. Results: The Manufacturers and User Defined Experience search identified 105 leads that had inside-out insulation defects. Eight-French single-coil Riata leads accounted for a higher-than-expected proportion (25.7%) of the leads with this defect. A total of 226 insulation defects were found in the 105 leads (2.2 defects per lead), including 143 inside-out defects (1.4 defects per lead). The most common location of insulation defects was distal to the proximal coil (n = 108). Twenty-eight leads (26.7%) had inside-out insulation defects underneath the shocking coils. Of 43 leads whose cables were assessed for the integrity of the ethylene-tetrafluoroethylene cable coating, 22 (51.2%) were found to be abraded, exposing the conductor surfaces. On X-ray radiography or fluoroscopy, 7 leads were found to have externalized cables; 2 of these leads had no electrical abnormalities, while 4 exhibited noise or increased impedance. Inappropriate shocks were experienced by 31 of the 105 patients (29.5%). Conclusion: Riata leads that have inside-out insulation defects often have multiple defects, including additional inside-out abrasions along the body of the lead and beneath the shocking coils. Eight-French single-coil Riata models may be more prone to externalized cables than are dual-coil and 7-F designs. Externalized cables are but one manifestation of interior insulation damage. Our findings question the durability of the ethylene-tetrafluoroethylene cable coating on exposed cables.

In Memory: John Boineau, MD - Uncorrected Proof

Richard B. Schuessler — 2011-12-29

John P. Boineau, MD, professor of surgery, of medicine, and of biomedical engineering at Washington University in St Louis, died on Monday, November 7, 2011, at Barnes-Jewish Hospital after a long battle with leukemia. He was 78.

Gap junctions, stem cells, and cell therapy: Rhythmic/arrhythmic implications - Uncorrected Proof

Leonid Maizels, Lior Gepstein — 2011-12-26

Gap junctions play a critical role in numerous cellular processes such as electrical coupling; ionic and molecular transfer between cells; control of cell differentiation, proliferation and migration, and cell metabolism; and even carcinogenesis. In cardiomyocytes, intact cell-to-cell coupling via gap junctions is crucial for the physiological cardiac electrical activation. Many disease states involve gap-junction remodeling, and abnormal cardiomyocyte coupling may be associated with the development of different arrhythmias.

Real-time magnetic resonance guidance of interventional electrophysiology procedures with passive catheter visualization and tracking - Uncorrected Proof

Peter Nordbeck, Harald H. Quick, Mark E. Ladd, Oliver Ritter — 2011-12-21

One of the key problems in interventional electrophysiology (EP) today is the inability to generate sufficient soft tissue contrast for intraprocedural visualization of the myocardium and the surrounding tissue by using conventional imaging techniques. Intraprocedural magnetic resonance imaging (MRI) has been identified as a potential solution to address this weakness of conventional EP; however, clinical adoption of MR-guided EP requires the development of EP devices that are both fully MR functional and MR safe at the same time. While recent technical improvements have shown the general potential to solve these problems, additional characteristics of the EP devices and MRI techniques become central. In particular, the mechanisms providing image contrast in MRI typically either induce large image artifacts around the catheters or make them nearly invisible. Therefore, additional active catheter visualization techniques have been proposed inevitably. In contrast, matching catheter and pulse sequence design might also be feasible to enable passive catheter visualization and tracking and could actually even allow better catheter functionality and real-time image quality by avoidance of technical cross talk and complications arising from additional technical equipment. Image contrast achievable by implementation of such an approach is demonstrated in the accompanying and , showing representative steady-state free precession–based real-time imaging sequences for MR-guided mapping of the right atrium and ventricle in an animal model (mini pig weighting 55 kg). Imaging was performed on a 1.5-T Philips Intera whole-body MR scanner with a thoracic multichannel array. A custom steerable EP catheter with full diagnostic and radiofrequency ablation capability (Biotronik/VascoMed, Germany) specifically designed for use in the MRI environment was used in combination with a catheter-optimized passive catheter visualization technique. The arrows in the figure indicate the advancing catheter tip during mapping in the right atrium and ventricle. An in-plane resolution of 1 mm and a slice thickness of 6 mm were used. The steady-state free precession imaging sequence presented here provides high temporal resolution at a frame rate of 4 frames/s. The combination of inherent bright blood contrast in steady-state free precession with the dark appearance of the passive catheter provides fast instrument tracking with optimized instrument-to-background contrast. However, owing to the lack of an active catheter tracking system in the presented MR-EP setup, attentive manual image plane selection during an intervention is demanded, which can sometimes be challenging. Combining imaging techniques for simultaneous tissue and catheter visualization, catheter tracking, monitoring of ablation, and assessment of the ablation lesions is assumed to provide decisive advantages over conventional EP and uniquely position MR-guided EP for complex interventions in the near future.

Connexin 43 and NaV1.5: Partners in crime? - Uncorrected Proof

Carol Ann Remme — 2011-12-19

Propagation of the electrical impulse through the myocardium depends on the critical interplay of various factors, including excitability, cell-to-cell coupling, and tissue architecture. Although intercellular transfer of current through gap junctions is essential for proper impulse propagation, mild-to-moderate reduction of the ventricular gap junctional protein connexin 43 (Cx43) is generally well tolerated by the normal, uncompromised heart. Indeed, transgenic mice with 50% reduction of Cx43 display normal ventricular activation patterns and conduction velocities, while conduction slowing and increased arrhythmia susceptibility is observed only in those mice in which Cx43 levels are reduced by more than 90%. In the ischemic and failing myocardium, however, heterogeneous reduction in Cx43 expression contributes to conduction abnormalities and arrhythmogenesis. Thus, Cx43 reduction appears to be detrimental only when severely or heterogeneously suppressed or in the presence of additional contributing factors, such as structural abnormalities and/or reduced tissue excitability. This concept is further highlighted in the current issue of HeartRhythm by the study of Jansen et al on ventricular arrhythmias in mice with a postnatally induced severe reduction in Cx43. More importantly, this study also implicates a modulatory effect of Cx43 on the expression and function of cardiac sodium channels, further underlining the increasing complex role of connexins.

Percutaneous extraction of stented device leads - Uncorrected Proof

2011-12-19

Background: There are limited published data regarding the safety and feasibility of extracting device leads jailed by a venous stent. Objective: •••. Methods: We present our experience percutaneously extracting 7 chronically implanted device leads jailed to the wall of the left innominate and/or subclavian veins by a previously placed stent. Results: All leads were successfully extracted by using a percutaneous approach. Both pacing leads and defibrillator leads were extracted. The oldest pacing lead extracted was 14 years old. The oldest defibrillator lead extracted was 6 years old. Three of the leads were extracted with simple manual traction alone. The 4 remaining leads required a more complex, femoral extraction approach for successful removal. Conclusion: No major complications were associated with the extraction procedures.

Potential mechanisms underlying the effect of gender on response to cardiac resynchronization therapy: Insights from the SMART-AV multicenter trial - Uncorrected Proof

2011-12-19

Background: Recent studies demonstrate that women may respond more favorably to cardiac resynchronization therapy (CRT) than do men. The mechanisms remain unclear. Objectives: To describe the effects of gender on response to CRT and to explore potential mechanisms behind these differences. Methods: Data for 846 patients from the SMART-AV trial were used to evaluate the mechanisms behind the effects of gender on CRT response. Atrioventricular optimization (AVO) was performed via SmartDelay or echocardiography. Baseline and 6-month left ventricular end systolic volume index (LVESVi) were fitted to a linear regression model with gender predicting change in LVESVi and adjusted for baseline covariates significantly differing by gender. The interaction variable for AVO and gender was also assessed for its effect on change in LVESVi. Results: Baseline variables, including age, body mass index, left ventricular ejection fraction, QRS width, and severity of heart failure symptoms, were comparable between men and women. Women had a higher incidence of left bundle branch block conduction and nonischemic cardiomyopathy and exhibited greater reductions in LVESVi even after adjustment for these differences (13.4 mL/m2 vs 8.5 mL/m2; P = .002). In addition, women had greater percentages of biventricular pacing and appeared to derive greater reductions in left ventricular volume with AVO than did men. Conclusions: Women demonstrated greater reductions in LVESVi with CRT than did men. These observations are not explained by differences in baseline characteristics. Greater degrees of biventricular pacing and enhanced response to AVO in women may partly explain the reason for the gender effect on CRT response.

Incidence and predictors of short- and long-term complications in pacemaker therapy: The FOLLOWPACE study - Uncorrected Proof

2011-12-19

Background: ••• Objective: To assess the incidence and determinants of short- and long-term complications after first pacemaker (PM) implantation for bradycardia. Methods: A prospective multicenter cohort study (the FOLLOWPACE study) among 1517 patients receiving a PM was conducted between January 2003 and November 2007. The independent association of patient and implantation-procedure characteristics with the incidence of PM complications was analyzed by using multivariable Cox regression analysis. Results: A total of 1517 patients in 23 Dutch PM centers were followed for a mean of 5.8 years (SD 1.1), resulting in 8797 patient-years. Within 2 months, 188 (12.4%) patients developed PM complications. Male gender, age at implantation, body mass index, a history of cerebrovascular accident, congestive heart failure, use of anticoagulant drugs, and passive atrial lead fixation were independent predictors for complications within 2 months, yielding a c index of 0.62 (95% confidence interval 0.57–0.66). Annual hospital implanting volume did not additionally contribute to the prediction of short-term complications. Thereafter, 140 (9.2%) patients experienced complications, mostly lead-related complications (n = 84). Independent predictors for long-term complications were age, body mass index, hypertension, and a dual-chamber device, yielding a c index of 0.62 (95% confidence interval 0.57–0.67). The occurrence of a short-term PM complication was not predictive of future PM complications. Conclusions: Complication incidence in modern pacing therapy is still substantial. Most complications occur early after PM implantation. Although various patient- and procedure-related characteristics are independent predictors for early and late complications, their ability to identify the patient at high risk is rather poor. This relatively high incidence of PM complications and their poor prediction underscores the usefulness of current guidelines for regular follow-up of patients with PM.

Exercise-induced vasospasm and the J-wave syndrome - Uncorrected Proof

2011-12-19

We report the case of a 63-year-old man with multiple cardiovascular risk factors who underwent stent implantation in proximal left anterior descending coronary artery in August 2008 because of unstable angina and 1-vessel disease. Two years later, the patient was referred again to our department because of symptoms of exercise-induced typical angina pectoris. Repeated coronary angiography revealed stent stenosis that was treated with a drug-eluting stent involving ostium and proximal left anterior descending coronary artery, and the patient was discharged on medical therapy. In July 2010, he presented atypical episodes of chest pain and a bicycle exercise test (World Health Organization protocol) was performed on admission. After normal baseline electrocardiographic (ECG) recording, a clear generalized J wave (arrowheads) progressively developed at 6 minutes of exercise (100 W). These changes were more evident in inferior leads (, middle panel) with mirror-shaped changes in aVL and right precordial leads. J-wave amplitude slightly increased during ongoing exercise, leading to repetitive, nonsustained polymorphic ventricular tachycardias (, left panel) with associated hypotensive response and near-syncope. On immediate exercise cessation, ventricular arrhythmias progressively disappeared in the next minutes and giant J waves with coved-type ST-segment elevation were clearly observed in inferior leads and V3-V6 with reciprocal ST-segment depression (, left panel). These changes spontaneously evolved to a saddleback appearance and progressively disappeared with complete resolution (, middle panel). A repeat coronary angiography with intravascular ultrasound imaging was then performed, revealing no significant coronary lesions. Resting systolic left ventricular function has always been entirely normal. Serum ion levels were normal. It was assumed that coronary vasospasm might have been responsible for the current symptoms and exercise response. Therefore, treatment with calcium antagonist (diltiazem 200 mg bid) and nitrates was commenced. A repeat exercise test under this treatment was uneventful (, right panel), and an implantable cardioverter-defibrillator was indicated prior to discharge. During 13-month follow-up, the patient was asymptomatic and no arrhythmic events were registered in the device memory.

Six uneventful years with a pacing lead in the left ventricle - Uncorrected Proof

Lee Fong Ling, Harry Lever — 2011-12-15

A 61-year-old asymptomatic man was referred to our institution for surgical repair of an aortic root aneurysm. His medical history was significant for mechanical aortic valve replacement 9 years ago, subsequent long-term anticoagulation, and dual-chamber pacemaker implantation for heart block 6 years ago. A preoperative electrocardiogram (A) showed a right bundle branch block pattern of paced beats that raised the suspicion of lead malposition in the left ventricle (LV). Lateral (B) and posteroanterior (C) chest radiography further confirmed the diagnosis. On the lateral chest radiography, the ventricular lead (arrow) appeared to point in the “correct” direction toward the right ventricular apex but was positioned rather posteriorly. Transthoracic echocardiogram revealed that the ventricular lead was visualized to cross the interatrial septum via the foramen ovale (D, arrow, and movie clip in the ) from the right atrium and passed through the left atrium and the mitral valve and inserted into the left ventricular lateral wall. During his aortic root surgery, thrombus formation was found along the left ventricular lead. The left ventricular lead was removed and replaced with an epicardial lead.

The reality of implantable cardioverter-defibrillator longevity: What can be done to improve cost-effectiveness? - Uncorrected Proof

Andrea M. Russo — 2011-12-14

Multiple clinical trials have demonstrated the mortality benefit of implantable cardioverter-defibrillator (ICD) therapy for the primary prevention of sudden cardiac death, expanding the indications for device therapy. However, ICDs are expensive and patient longevity often exceeds pulse generator longevity, and so many patients will require replacement of pulse generators, which is associated with additional costs. Generator replacement also carries a substantial risk for complications even when performed electively. While the overall risk of initial implantation complications is 3.2% in the National Cardiovascular Data Registry ICD Registry, the risk of major complications for generator replacements is 4.1%–5.8%, with complications including death. Risks are even higher for patients undergoing system upgrade, and risks of pocket-related adverse events requiring surgical intervention increase with every consecutive replacement. Therefore, it is beneficial to reduce the need for upgrade or replacement of pulse generators.

Unpredictable battery depletion of St Jude Atlas II and Atlas+ II HF implantable cardioverter-defibrillators - Uncorrected Proof

2011-12-14

Background: Predictable progression to battery depletion is necessary for device management in patients with pacemakers or implantable cardioverter-defibrillators, particularly in patients who either are pacemaker dependent or have required implantable cardioverter-defibrillator therapies. Objective: To determine the incidence and characteristics of unexpected battery depletion in patients implanted with a cardiac resynchronization therapy – defibrillator (CRT-D) device. Methods: All patients with a St Jude Atlas+ HF or Atlas II HF CRT-D device implanted between 2004 and 2007 at the Massachusetts General Hospital and the Nashville VA Medical Center (Vanderbilt University) were studied. All patients with early generator depletion (transition of generator voltage above specified elective replacement indicator [ERI] to end of life [EOL] in less than 90 days) were evaluated further. Results: Eight cases (mean age 69.6 ± 9 years) with abrupt battery depletion were identified among 191 patients (4.2%) implanted with a St Jude Atlas CRT-D device. The longevity of 8 premature depletion devices was 46.4 ± 10 months (median 45 months). The battery voltage in these 8 devices decreased from a mean of 2.48 ± 0.03 V (above ERI) to 2.3 ± 0.08 V (below ERI) over 33.3 ± 23 days (range 1–59 days; median 38.5 days). One device reached EOL status within 1 day of having battery voltage above ERI and another device within 12 days. Conclusion: The incidence of abrupt battery depletion was 4.2% in patients implanted with a St Jude Atlas CRT-D device. No common mechanism has been identified for this failure. Close monitoring of battery voltage and timely generator replacement are required in patients with these devices.

Effect of electrocardiographic lead placement on localization of outflow tract tachycardias - Uncorrected Proof

Elad Anter, David S. Frankel, Francis E. Marchlinski, Sanjay Dixit — 2011-12-12

Background: The origin of outflow tract ventricular tachycardia (OTVT) can be predicted from a surface electrocardiogram: indexes of R-wave amplitudes in leads V1 and V2 are used to differentiate a right origin from a left origin, while the axis of lead I differentiates an anterior origin from a posterior origin. Incorrect electrode placement is clinically common and may alter predictability of OTVTs. Objective: To explore the influence of vertical deviation in leads V1 and V2 and arm lead position on the QRS morphology of OTVTs. Methods: Vertical deviation of leads V1 and V2 was studied in 18 patients with OTVTs. Ventricular premature depolarization beats were recorded in the standard position, superior position, and inferior position. The effect of arm lead position was studied in a separate cohort of 16 patients: ventricular premature depolarizations were recorded with limb leads positioned over the shoulders and over the chest. The origin of tachycardia was determined by using activation mapping and confirmed by successful ablation. Results: Superior displacement of leads V1 and V2 reduced the R-wave amplitude and led to a decreased R/S ratio (0.11 ± 0.09 vs 0.17 ± 0.1; P <.01), while inferior displacement of leads V1 and V2 resulted in an increased R-wave amplitude and led to an increased R/S ratio (0.46 ± 0.35 vs 0.17 ± 0.1; P <.01). Anterior displacement of the arm leads from shoulders to chest resulted in the reduction in the R-wave amplitude in lead I (0.25 ± 0.30 mV vs 0.04 ± 0.43 mV; P <.05). Conclusions: Small changes in electrocardiographic electrode placement markedly alter the QRS morphology of OTVTs and thus alter the predictability of OTVT origin. These deviations are well within the range of clinical application and have the potential to misdirect ablation procedures.

SCN1Bb R214Q found in 3 patients: 1 with Brugada syndrome and 2 with lone atrial fibrillation - Uncorrected Proof

Morten S. Olesen, Anders G. Holst, Stig Haunsø, Jacob Tfelt-Hansen — 2011-12-08

Background: SCN1Bb encodes the β-subunit of the sodium channel. A mutation in SCN1Bb R214Q has recently been shown both to increase the Kv4.3 current and to decrease the sodium current. The variant was suggested to increase the susceptibility to Brugada syndrome (BrS). Objective: To sequence a population of BrS and early-onset lone atrial fibrillation (AF) patients for the R214Q mutation in the SCN1Bb gene. Methods: The coding sequence and splice junctions of SCN1Bb were bidirectionally sequenced by using Big Dye chemistry in 192 early-onset lone AF patients and 22 BrS patients. Results: Three probands carrying the R214QC variant were identified. No mutations were identified in genes previously associated with BrS or AF in these patients. Case 1 was a BrS patient with a type 1 electrocardiogram and onset of disease at the age of 54 years. Case 2 was a lone AF case with onset at the age of 39 years and paroxysmal lone AF. Case 3 also had the onset of persistent lone AF at the age of 39 years. Both lone AF patients had electrocardiograms that raised the suspicion of BrS, but intravenous flecainide testing was, in both cases, negative. R214Q was not present in the control group (n = 216) and has not previously been reported in conjunction to AF. Conclusion: Three patients of 192 young lone AF and 22 BrS patients carried the nonsynonymous R214Q mutations in SCN1Bb, thereby indicating that this variant increases the susceptibility to both BrS and AF.