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Torsades de Pointes (TdP) refers to a polymorphic ventricular tachycardia (VT) with undulating QRS axis that occurs in long QT syndrome (LQTS), although the term has been used to describe polymorphic ventricular tachyarrhythmias in which QT intervals are not prolonged, such as short-coupled variant of TdP currently known as short-coupled ventricular fibrillation (VF) and Brugada syndrome. Extensive works on LQTS-related TdP over more than 50 years since it was first recognized by Dessertennes who coined the French term meaning “twisting of the points”, have led to current understanding of the electrophysiological mechanism that TdP is initiated by triggered activity due to early afterdepolarization (EAD) and maintained by reentry within a substrate of inhomogeneous repolarization. While a recently emerging notion that steep voltage gradients rather than EADs are crucial to generate premature ventricular contractions provides additions to the initiation mode, the research to elucidate the maintenance mechanism hasn't made much progress. The reentrant activity that produces the specific form of VT is not well characterized. We have conducted optical mapping in a rabbit model of electrical storm by electrical remodeling (QT prolongation) due to chronic complete atrioventricular block and demonstrated that a tissue-island with prolonged refractoriness due to enhanced late Na+ current (INa−L) contributes to the generation of drifting rotors in a unique manner, which may explain the ECG characteristic of TdP. Moreover, we have proposed that the neural Na+ channel NaV1.8-mediated INa−L may be a new player to form the substrate for TdP. Here we discuss TdP mechanisms by comparing the findings in electrical storm rabbits with recently published studies by others in simulation models and human and animal models of LQTS.

Congenital long QT syndrome (LQTS) carries an increased risk for syncope and sudden death. QT prolongation promotes ventricular extrasystoles, which, in the presence of an arrhythmia substrate, might trigger ventricular tachycardia degenerating into fibrillation. Increased electrical heterogeneity (dispersion) is the suggested arrhythmia substrate in LQTS. In the most common subtype LQT1, physical exercise predisposes for arrhythmia and spatiotemporal dispersion was therefore studied in this context. Thirty-seven patients (57% on b-blockers) and 37 healthy controls (mean age, 31 vs. 35; range, 6--68 vs. 6--72 yr) performed an exercise test. Frank vectorcardiography was used to assess spatiotemporal dispersion as Tampl, Tarea, the ventricular gradient (VG), and the Tpeak-end interval from 10-s signal averages before and 7 ± 2 min after exercise; during exercise too much signal disturbance excluded analysis. Baseline and maximum heart rates as well as estimated exercise intensity were similar, but heart rate recovery was slower in patients. At baseline, QT and heart rate-corrected QT (QTcB) were significantly longer in patients (as expected), whereas dispersion parameters were numerically larger in controls. After exercise, QTpeakcB and Tpeak-endcB increased significantly more in patients (18 ± 23 vs. 7 ± 10 ms and 12 ± 17 vs. 2 ± 6 ms; P < 0.001 and P < 0.01). There was, however, no difference in the change in Tampl, Tarea, and VG between groups. In conclusion, although temporal dispersion of repolarization increased significantly more after exercise in patients with LQT1, there were no signs of exercise-induced increase in global dispersion of action potential duration and morphology. The arrhythmia substrate/mechanism in LQT1 warrants further study. [ABSTRACT FROM AUTHOR]

Background: Bidirectional ventricular tachycardia (BVT) is a rare type of ventricular tachycardia that is characterized by a beat-to-beat alternation in the QRS axis. Previous studies have shown that it is caused by alternating focal activities from 2 locations., Objective: This study proposes a novel mechanism for the formation of spatially discordant alternans (SDA) due to the periodic pacing site alternation that occurs in BVT., Methods: We used mathematical models of cardiac tissue to understand the dynamic and physiologic mechanisms underlying SDA formation., Results: We found that SDA was formed by periodic pacing site alternation. When tissue was paced from 2 locations alternately, the timing of pacing at distant locations varied, creating a long-short-long-short sequence of pacing periods and thus action potential durations. Importantly, the nodal lines were perpendicular to the wavefront, which is more arrhythmogenic than when nodal lines are parallel to the wavefront. A positive correlation was observed between the separation distance of the 2 sites and the alternans amplitude. SDA patterns can be predicted from the tissue geometry and pacing site locations., Conclusion: Periodic pacing site alternation, which occurs in BVT, leads to arrhythmogenic SDA. The nodal lines associated with this phenomenon can be predicted on the basis of tissue geometry and focal locations., Competing Interests: Disclosures The authors have no conflicts of interest to disclose., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

The incidence of atrial fibrillation (AF) in Brugada syndrome (BrS) has been reported at between 9% and 53% by different series, but the true prevalence is unknown. However, AF may be the presenting feature in some patients. The underlying mechanisms for AF may be a combination of multiple factors, genetic or acquired, that may impact upon autonomic function, atrial structure, and conduction velocities or other unknown factors. The presence of AF has been associated with a more malignant course, with a greater incidence of syncope and ventricular arrhythmias, thus acting as marker of more advanced disease. Regarding the management of patients with AF, antiarrhythmic drugs effective in preventing malignant arrhythmias in BrS such as quinidine or invasive treatment with pulmonary vein isolation (PVI) may be useful in AF treatment. In this review, we aim to present the current perspectives regarding the genetics, pathophysiology, management, and prognosis of AF in patients with BrS. [ABSTRACT FROM AUTHOR]

Torsades de Pointes (TdP) refers to a polymorphic ventricular tachycardia (VT) with undulating QRS axis that occurs in long QT syndrome (LQTS), although the term has been used to describe polymorphic ventricular tachyarrhythmias in which QT intervals are not prolonged, such as short-coupled variant of TdP currently known as short-coupled ventricular fibrillation (VF) and Brugada syndrome. Extensive works on LQTS-related TdP over more than 50 years since it was first recognized by Dessertennes who coined the French term meaning "twisting of the points", have led to current understanding of the electrophysiological mechanism that TdP is initiated by triggered activity due to early afterdepolarization (EAD) and maintained by reentry within a substrate of inhomogeneous repolarization. While a recently emerging notion that steep voltage gradients rather than EADs are crucial to generate premature ventricular contractions provides additions to the initiation mode, the research to elucidate the maintenance mechanism hasn't made much progress. The reentrant activity that produces the specific form of VT is not well characterized. We have conducted optical mapping in a rabbit model of electrical storm by electrical remodeling (QT prolongation) due to chronic complete atrioventricular block and demonstrated that a tissue-island with prolonged refractoriness due to enhanced late Na + current (I Na-L ) contributes to the generation of drifting rotors in a unique manner, which may explain the ECG characteristic of TdP. Moreover, we have proposed that the neural Na + channel Na V 1.8-mediated I Na-L may be a new player to form the substrate for TdP. Here we discuss TdP mechanisms by comparing the findings in electrical storm rabbits with recently published studies by others in simulation models and human and animal models of LQTS., Competing Interests: YT and MS are affiliated with a department sponsored by BIOTRONIK Japan Inc., Japan Lifeline Co., Ltd., Fukuda Denshi Co., Ltd., and Suzuken Co., Ltd., and SY with a department sponsored by Medtronic Japan Co., Ltd. The remaining authors have no relationships relevant to the contents of this paper to disclose., (© 2024 Tsuji, Yamazaki, Shimojo, Yanagisawa, Inden and Murohara.)

A 77-year-old man with ischemic cardiomyopathy and a cardiac resynchronization therapy-defibrillator (CRT-D) device came to our attention due to incessant ventricular tachycardia and multiple implantable cardioverter defibrillator (ICD) shocks. An electrocardiogram showed non-sustained monomorphic ventricular tachycardias (NSVTs) constantly occurring after each biventricular stimulation. During an electrophysiological study, NSVTs reproducibly recurred only after right ventricular (RV) pacing; LV pacing did not induce any NSVTs. The activation map was consistent with a localized reentry at the interventricular septum, and a double exit; at the LV exit site, a single radiofrequency energy application immediately interrupted the occurrence of the NSVTs. Current evidence supports LV pacing to be pro-arrhythmogenic in few CRT patients. This unusual case shows that RV pacing during CRT could produce frequent ventricular arrhythmias and arrhythmic storm. Catheter ablation can be considered an effective therapeutic option, especially when CRT maintenance is highly advisable.

A 77-year-old man with ischemic cardiomyopathy and a cardiac resynchronization therapy-defibrillator (CRT-D) device came to our attention due to incessant ventricular tachycardia and multiple implantable cardioverter defibrillator (ICD) shocks. An electrocardiogram showed non-sustained monomorphic ventricular tachycardias (NSVTs) constantly occurring after each biventricular stimulation. During an electrophysiological study, NSVTs reproducibly recurred only after right ventricular (RV) pacing; LV pacing did not induce any NSVTs. The activation map was consistent with a localized reentry at the interventricular septum, and a double exit; at the LV exit site, a single radiofrequency energy application immediately interrupted the occurrence of the NSVTs. Current evidence supports LV pacing to be pro-arrhythmogenic in few CRT patients. This unusual case shows that RV pacing during CRT could produce frequent ventricular arrhythmias and arrhythmic storm. Catheter ablation can be considered an effective therapeutic option, especially when CRT maintenance is highly advisable. [ABSTRACT FROM AUTHOR]

Background Variable success rates have been reported after epicardial radiofrequency catheter ablation (RFA) in arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C). The details of the electroanatomic substrate are limited to a few studies, and the characteristics of the recurrent ventricular tachycardia (VT) in ARVD/C remain largely unknown. Objective The purpose of this study was to report procedural strategy, safety, and efficacy of epicardial RFA at a tertiary single center with a focus on the characteristics of the substrate and recurrent VT. Methods We included 30 ARVD/C patients (mean age 33.1 ± 11.1 years, 53% male) who underwent endocardial/epicardial mapping and epicardial catheter ablation of VT at the Johns Hopkins Hospital. Implantable cardioverter-defibrillator interrogations were evaluated for VT recurrence. Results The majority of critical VT circuits (69%) were on the epicardial surface, mostly in the subtricuspid region. Eight patients (27%) experienced VT recurrence after epicardial RFA, and the VT-free survival was 83%, 76%, and 70% at 6,12, and 24, months respectively. A significant reduction of VT burden was observed ( P <.001), even among those with VT recurrence. No complications occurred except for acute pericarditis in 1 patient. The majority of VT recurrences occurred during the first year after RFA, during exercise, had fast cycle lengths, and required implantable cardioverter-defibrillator shock for termination. Conclusion The vast majority of critical VT circuits were epicardial, mostly in the subtricuspid region. Epicardial RFA of VT appears to be both safe and effective in achieving arrhythmia control in ARVD/C. The features of the recurrent VT suggest a possible catecholamine-mediated mechanism with an origin in a region not targeted for ablation. [ABSTRACT FROM AUTHOR]

Introduction: There is no universally accepted method by which to diagnose clinical ventricular tachycardia (VT) due to cAMP-mediated triggered activity. Based on cellular and clinical data, adenosine termination of VT is thought to be consistent with a diagnosis of triggered activity. However, a major gap in evidence mitigates the validity of this proposal, namely, defining the specificity of adenosine response in well-delineated reentrant VT circuits. To this end, we systematically studied the effects of adenosine in a model of canine reentrant VT and in human reentrant VT, confirmed by 3-dimensional, pace- and substrate mapping. Methods and Results: Adenosine (12 mg [IQR 12-24]) failed to terminate VT in 31 of 31 patients with reentrant VT due to structural heart disease, and had no effect on VT cycle length (age, 67 years [IQR 53-74]); ejection fraction, 35% [IQR 20-55]). In contrast, adenosine terminated VT in 45 of 50 (90%) patients with sustained focal right or left outflow tract tachycardia. The sensitivity of adenosine for identifying VT due to triggered activity was 90% (95% CI, 0.78-0.97) and its specificity was 100% (95% CI, 0.89-1.0). Additionally, reentrant circuits were mapped in the epicardial border zone of 4-day-old infarcts in mongrel dogs. Adenosine (300-400 μg/kg) did not terminate sustained VT or have any effect on VT cycle length. Conclusion: These data support the concept that adenosine's effects on ventricular myocardium are mechanism specific, such that termination of VT in response to adenosine is diagnostic of cAMP-mediated triggered activity. [ABSTRACT FROM AUTHOR]

Abstract: Heart failure is the final common pathway of various cardiac pathologies and is associated with sudden cardiac death, mostly caused by ventricular arrhythmias. In this paper we briefly review the electrophysiological remodeling and the alterations in intracellular calcium handling, and the resulting arrhythmogenic mechanisms associated with heart failure. Intercellular uncoupling and fibrosis are identified as a major arrhythmogenic factors. Diet and ventricular wall stretch are discussed as modulating factors. Finally, emphasis is placed on the hitherto poorly studied aspects of right ventricular failure. This article is part of a Special Issue entitled: Heart failure pathogenesis and emerging diagnostic and therapeutic interventions. [Copyright &y& Elsevier]

The article reports that mutations in sarcolemmal membrane-associated protein (SLMAP) may cause Brugada syndrome by modulating the intracellular trafficking of hNav1.5 channel. The authors analyzed 190 unrelated patients with Brugada syndrome for mutations in SLMAP. Results showed the mutations affected the membrane surface expression of hNav1.5 in the transfected cells. Also, silencing of mutant SLMAP by small interfering RNA rescued the surface expression of hNav1.5.

Atrioventricular nodal reentrant tachycardia (AVNRT) is the most common and complex form of regular narrow QRS complex tachycardia. AVNRT most frequently occurs in the adults, and women are more commonly affected. The tachycardia results from disturbed impulse propagation, both in the intact and structurally diseased hearts. Initially the AVNRT reentry circuit was thought to be situated in the AV node. However, anatomical, histological as well as electrophysiological studies resulted in evolution of knowledge from the concept of AV node dualism to its multilevel architectonics. Next years have shown that AVNRT circuit involves larger areas, including atrioventricular junction, adjacent atrial structures and in particular so called atrial inputs, including at least antero-superior and postero-inferior entries, and, occasionally, the left atrial entry. We have explained the multiplicity of this arrhythmia, its anatomical and pathophysiological models. We have discussed treatment approaches, including methods of termination as well as invasive treatment using RF ablation. In addition, we have presented factors influencing decision making process and indications for RF ablation in subjects with AVNRT. [ABSTRACT FROM AUTHOR]

Background: Bidirectional ventricular tachycardia (BVT), which is characterized by an alternating beat-to-beat ECG QRS axis, is a rare but intriguing arrhythmia associated with digitalis toxicity, familial catecholaminergic polymorphic ventricular tachycardia (CPVT), and several other conditions that predispose cardiac myocytes to delayed afterdepolarizations (DADs) and triggered activity. Evidence from human and animal studies attributes BVT to alternating ectopic foci originating from the distal His–Purkinje system in the left and/or right ventricle, respectively. Objective: The purpose of this study was to evaluate a simple “ping pong” model of reciprocating bigeminy to explain BVT. Methods: We constructed a two-dimensional anatomic model of the rabbit ventricles with a simplified His–Purkinje system, in which different sites in the His–Purkinje system had different heart rate thresholds for DAD-induced bigeminy. Results: When the heart rate exceeded the threshold for bigeminy at the first site in the His–Purkinje system, ventricular bigeminy developed, causing the heart rate to accelerate and exceed the threshold for bigeminy at the second site. Thus, the triggered beat from the first site induced a triggered beat from the second site. The triggered beat from the second site next reciprocated by inducing a triggered beat from the first site, and so forth. Bigeminy from two sites produced BVT, and that from three or more sites produced polymorphic VT. Conclusion: This “ping pong” mechanism of reciprocating bigeminy readily produces the characteristic ECG pattern of BVT and its degeneration to polymorphic VT if additional sites develop bigeminy. [Copyright &y& Elsevier]

Abstract: Atrial fibrillation (AF) remains the most common clinically encountered arrhythmia. Unlike supraventricular arrhythmias that use a defined mechanism, AF involves a wide spectrum of arrhythmias from lone AF to paroxysmal to chronic AF. AF is an arrhythmia that may develop in several ways. Mechanical remodeling manifests as decreased atrial contractility and increased atrial compliance which leads to a stretch of the atrial myocardium. Atrial remodeling may also increase in atrial fibrosis which can slow conduction velocity and can shorten the refractory period in atria with long-standing AF. It is still unclear whether initiation of AF activates direct inflammatory effects or whether the presence of a pre-existing systemic inflammatory state promotes further persistence of AF. Currently, the patient population undergoing AF ablation has greatly expanded. Patients are older and have larger left atrial size and are more likely to have persistent/permanent AF. It is likely that AF comprises a spectrum of disease with no single mechanism adequate enough to comprehensively explain AF and its variability. The management of patients with AF involves elements of anticoagulation, rate control and rhythm control and such treatment strategies are not necessarily mutually exclusive of each other. [Copyright &y& Elsevier]

Background: Quinidine is used to treat atrial fibrillation and ventricular arrhythmias. However, at low concentrations, it can induce torsade de pointes (TdP). Objective: The purpose of this study was to examine the role of late sodium current (INa) as a modulator of the arrhythmogenicity of quinidine in female rabbit isolated hearts and cardiomyocytes. Methods: Epicardial and endocardial monophasic action potentials (MAPs), ECG signals, and ion channel currents were measured. The sea anemone toxin ATX-II was used to increase late INa. Results: Quinidine had concentration-dependent and often biphasic effects on measures of arrhythmogenicity. Quinidine increased the duration of epicardial MAP (MAPD90), QT interval, transmural dispersion of repolarization (TDR), and ventricular effective refractory period. Beat-to-beat variability of MAPD90 (BVR), the interval from peak to end of the T wave (Tpeak-Tend) and index of Tpeak-Tend/QT interval were greater at 0.1 to 3 μmol/L than at 10–30 μmol/L quinidine. In the presence of 1 nmol/L ATX-II, quinidine caused significantly greater concentration-dependent and biphasic changes of Tpeak-Tend, TDR, BVR, and index of Tpeak-Tend/QT interval. Quinidine (1 μmol/L) induced TdP in 2 and 13 of 14 hearts in the absence and presence of ATX-II, respectively. Increases of BVR, index of Tpeak-Tend/QT interval, and Tpeak-Tend were associated with quinidine-induced TdP. Quinidine inhibited IKr, peak INa, and late INa with IC50s of 4.5 ± 0.3 μmol/L, 11.0 ± 0.7 μmol/L, and 12.0 ± 0.7 μmol/L. Conclusion: Quinidine had biphasic proarrhythmic effects in the presence of ATX-II, suggesting that late INa is a modulator of the arrhythmogenicity of quinidine. Enhancement of late INa increased proarrhythmia caused by low but not high concentrations of quinidine. [Copyright &y& Elsevier]

Pulmonary veins (PVs) are the predominant sources of paroxysmal atrial fibrillation (AF), and electrical PV isolation has become an established interventional treatment for patients suffering from AF. There are a few cases describing PV tachycardias; however, mechanisms of PV arrhythmogenicity resulting in PV tachycardias remain incompletely understood. We report on a patient who underwent PV isolation for paroxysmal AF, in whom a persistent PV tachycardia was observed within an isolated vein. This tachycardia was stable in nature and different pacing manoeuvres revealed electrophysiological features consistent with reentry (Lasso displaying the entire tachycardia cycle length, concealed entrainment, overdrive termination, and induction by programmed stimulation) as the underlying mechanism. [ABSTRACT FROM PUBLISHER]

Background: Pulmonary vein (PV) ablation plays an important role in atrial fibrillation (AF) therapy but suffers from a limited mechanistic understanding of PV arrhythmogenicity. Rapid focal activation has been suggested, but some evidence points to underlying reentry.Objective: This study was performed to evaluate how the electrophysiological properties of PVs may make them a site for reentry and to analyze specifically the roles of PV dimensions and coupling properties.Methods: A computer model designed to efficiently reproduce electrophysiological behaviors was fit to action potentials from canine left atria (LA) and PVs. To assess structural and functional arrhythmogenic determinants, an idealized PV of varying length and circumference was attached to LA tissue, and 5 seconds of activity after extrastimulation were simulated.Results: PV reentrant activity depended critically on vein size and coupling properties. With cumulative removal of transverse and longitudinal connections, sustained (n=23) or nonsustained (n=93) reentries could be observed (687 simulations) for veins 1-3 cm long and 1-2 cm in circumference. The prevalence of sustained reentry increased with PV length (8% for 1 cm vs. 22% and 31% for 2 and 3 cm, respectively; P<.05 for each). The PV circumference did not affect the incidence of sustained reentry (25%, 17%, and 21% for 1-, 1.5-, and 2-cm circumferences; P=NS), but the number of reentrant events increased from 12/201 simulations for PVs with a 1-cm circumference to 48/232 and 56/254 events for PVs with 1.5- and 2-cm circumferences, respectively (P<.05). Sustained reentry cycle lengths were approximately 200-250 ms (16/23), except for the longest PVs.Conclusion: Reentry occurs readily in PVs with realistic properties in the context of specific connection heterogeneities. Reentry properties and incidence depend on PV anisotropy and dimensions but could certainly contribute significantly to PV arrhythmogenesis. [ABSTRACT FROM AUTHOR]

Aim: The primary aim of this study was to evaluate the utility of decremental ramp atrial extrastimuli pacing protocol (PRTCL) for induction of atrioventricular nodal re-entrant tachycardia (AVNRT), and other supraventricular tachycardias (SVTs), compared to standard (STD) methods. Methods: The study cohort of 121 patients (age 57.51 ± 14.02 years) who presented with documented SVTs and/or symptoms of palpitations and dizziness, and underwent invasive electrophysiological evaluation was divided into Group I (AVNRT, n = 42) and Group II (Control, n = 79). The PRTCL involved a train of six atrial extrastimuli, delivered in a decremental ramp fashion. The STD methods included continuous burst and rapid incremental pacing up to atrioventricular (AV) block cycle length, and single and occasionally double atrial extrastimuli. Prolongation in the Atrio-Hisian (Δ-AH) intervals achieved by both methods were compared, as were induction frequencies. Results: In Group I, three categories of responses—(1) induction of AVNRT, (2) induction of echo beats only, and (3) none—were observed in 29 (69%), 11 (26%), and 2 (5%) patients with the PRTCL, when compared with 14 (33%), 16 (38%), and 12 (29%) patients with STD methods in the baseline state without the use of pharmacological agents. The Δ-AH intervals for each of these three categories were larger using PRTCL versus STD methods; 293.3 ± 95.2 ms versus 192.9 ± 61.4 ms (P < 0.005), 308.6 ± 68.5 ms versus 189. 9 ± 64.9 ms (P < 0.0005), and 203.0 ± 86.3 ms versus 145.8 ± 58.9 ms (P = NS), respectively. In Group II, in one patient with dual AV nodal physiology but no clinical tachycardia, the PRTCL induced nonsustained (12 beats) AVNRT. Additionally, in this group, both PRTCL and STD methods induced atrial tachycardia in two patients and orthodromic AV re-entrant tachycardia in one patient. Conclusion: Decremental ramp atrial extrastimuli pacing PRTCL demonstrates a superior response for induction of typical AVNRT as compared to STD techniques. Because of easy and reliable induction of AVNRT and echo beats by the PRTCL, we recommend it as a method to increase the likelihood of induction of AVNRT. For induction of other SVTs, the PRTCL and the STD methods are comparable. [ABSTRACT FROM AUTHOR]

Introduction: The pulmonary veins (PVs) are a dominant source of triggers initiating atrial fibrillation (AF). While recent evidence implicates these structures in the maintenance of paroxysmal AF, their role in permanent AF is not known. The current study aims to compare the contribution of PV activity to the maintenance of paroxysmal and permanent AF. Methods and Results: Thirty-four patients with paroxysmal AF (n = 20) or permanent AF (n = 14) undergoing ablation were studied. Prior to ablation, 32 seconds of electrograms were acquired from each PV and the coronary sinus (CS). The frequency of activity of each PV and CS was defined as the highest amplitude frequency on spectral analysis. The effects of ablation on the AF cycle length (AFCL) and frequency and on AF termination were determined. Significant differences were observed between paroxysmal and permanent AF. Paroxysmal AF demonstrates higher frequency PV activity (11.0 ± 3.1 vs 8.8 ± 3.0 Hz; P = 0.0003) but lower CS frequency (5.8 ± 1.2 vs 6.9 ± 1.4 Hz; P = 0.01) and longer AFCL (182 ± 17 vs 158 ± 21 msec; P = 0.002), resulting in greater PV to atrial frequency gradient (7.2 ± 2.2 vs 4.2 ± 2.9 Hz; P = 0.006). PV isolation in paroxysmal AF resulted in a greater decrease in atrial frequency (1.0 ± 0.7 vs −0.05 ± 0.4 Hz; P < 0.0001), greater prolongation of the AFCL (49 ± 35 vs 5 ± 6 msec; P < 0.0001), and more frequent AF termination (11/20 vs 0/14; P = 0.0007) compared to permanent AF. Conclusion: Paroxysmal AF is associated with higher frequency PV activity and lesser CS frequency compared to permanent AF. Isolation of the PVs had a greater impact on the fibrillatory process in paroxysmal AF compared to permanent AF, suggesting that while the PVs have a role in maintaining paroxysmal AF, these structures independently contribute less to the maintenance of permanent AF. [ABSTRACT FROM AUTHOR]

The Fontan circulation has been a major success in the management of patients with functionally single-ventricle cardiac lesions, although arrhythmia remains one of the major complications in the long term and historically has been difficult to treat. The electrophysiologic substrate within the right atrium is complex, with areas of scarring and/or anatomic structures acting as central barriers to conduction in reentrant circuits, which may be mechanistically and anatomically different from typical atrial flutter. Developments in three-dimensional mapping have improved our understanding of different arrhythmia mechanisms, which is fundamental to developing a better strategy for arrhythmia ablation using percutaneous techniques. [Copyright &y& Elsevier]

Abstract: Electrophysiological remodeling of ion channels in heart failure causes action potential prolongation and plays a role in arrhythmia mechanism. The importance of down-regulation of potassium currents is well-known, but a role for Na current (I Na) in heart failure is less well established. We studied I Na in heart failure ventricular cells from a canine pacing model of heart failure and also from explanted failing human hearts. Peak I Na density was significantly decreased by 39% and 57% in the dog model and in human heart failure, respectively. The kinetics of peak I Na were not different in heart failure. Late I Na was measured 750 ms after the initial depolarization as the saxitoxin (STX)-sensitive current and also as the current remaining after contaminating currents were blocked. Late I Na as a percentage of the peak I Na was significantly increased in both conditions. In dogs, STX sensitive late I Na was 0.5 ± 0.1% n = 16 cells from eight normal hearts and 3.4 ± 1.4% n = 12 cells from seven failing hearts; in humans, it was 0.2 ± 0.1% n = 4 cells from two normal hearts and 2.4 ± 0.5% n = 10 cells from three human failing hearts (–40 mV). Quantitative measures of mRNA including RNase protection assays and real time quantitative PCR in the dog model showed no differences for different α subunit isoforms (NaV1.1, 1.3, 1.5) and for the β1 and β2 subunits. This suggests neither α subunit isoform switching nor altered β subunit expression is a mechanism for increased late I Na. We conclude that a peak I Na is decreased, and non-inactivating late I Na is increased in heart failure and this may contribute to action potential prolongation and the generation of arrhythmia. [Copyright &y& Elsevier]

Objective: Three-dimensional characterization of the ventricular repolarization by the T vector and T vector loop morphology in coronary artery disease (CAD), and their response to short-term (no flow) ischemia induced by coronary occlusion during a percutaneous intervention (PCI).Background: The risk for sudden cardiac death is increased in conditions of acute or permanently heterogeneous ventricular repolarization, for which ischemia is a risk factor.Methods: Fifty-six CAD patients without visible collateral circulation were studied during an elective single-vessel PCI, and 10 healthy controls twice at rest. T vector parameters (Televation, Tazimuth, and QRS-T angle), and T loop parameters (Tarea, Tavplan, and Teigenv) were measured by vectorcardiography. ST vector magnitude (ST-VM) and its change (STC-VM) were used for reference.Results: At rest, T vector loop morphology (Tarea, Teigenv) was significantly different in CAD patients and controls, while T vector angles did not separate the groups. Ischemia induced significant changes in T loop parameters in the entire CAD group, whereas in the LAD subgroup significant changes were seen also in T vector angle. The T loop morphology was significantly different at baseline and a more pronounced response to ischemia (Tarea) was seen in patients with, than in those without, a history of hypertension.Conclusion: T loop morphology, rather than the T vector angle, separated CAD patients from healthy controls. Coronary occlusion had significant impact on ventricular repolarization, as assessed by T vector and morphology analysis, and most prominently in the LAD group. Hypertensive patients appeared especially vulnerable to ischemia. [ABSTRACT FROM AUTHOR]

Sudden cardiac death forms a major cause of mortality. Myocardial ischemia-induced ventricular fibrillation (VF) is frequently the underlying mechanism. Ventricular arrhythmias arise in two distinct phases during the first hour of ischemia. The first, the 1A phase, has been extensively studied, and few studies relate to the 1B phase. The latter is associated with intercellular electrical uncoupling, mediated by decreased conductance of gap junction channels.Although the relation between gap junctional uncoupling and decreased conduction velocity appears clear under normoxic conditions, additional factors contribute to conduction slowing during ischemia, and VF occurs preferentially at moderate levels of uncoupling. A potential mechanism of arrhythmias depends on temporary electrotonic depression of intrinsically viable tissue by the large bulk of the ischemic zone. This causes conduction slowing and conduction block in the surviving layers, leading to arrhythmias. These arrhythmias then resolve with progression of uncoupling. It is unknown whether either accelerated uncoupling or maintenance of gap junctional communication is antiarrhythmic. Ischemic preconditioning postpones both gap junctional uncoupling and occurrence of VF. Given the burden of sudden death and the large number of casualties in the low-risk population, there is, even in the era of implantable cardiac defibrillators, need for further understanding the mechanism of ischemia-induced VF. [Copyright &y& Elsevier]

Introduction: The aim of this study was to determine if anisotropic action potential conduction was altered during development of left ventricular hypertrophy (LVH). Methods and Results: Isolated guinea pig left ventricular preparations from hearts that had developed LVH were used to measure conduction velocity in longitudinal and transverse orientations to the fiber direction. A variable degree of LVH was induced by placing a ring around the ascending aorta for 50 to 250 days. Results were compared with an age-matched control group that underwent a similar operation hut with no ring placement. LVH was measured as the heart-to-body-weight ratio (HBR), which correlated with an increase of mean myocyte cross-sectional area. Longitudinal conduction velocity (LCV) declined progressively as HBR increased (mean ± SD: sham vs LVH: HBR 3.74 ± 0.30 g/kg vs 4.53 ± 0.52 g/kg; LCV 72.8 ± 15.5 vs 63.6 ± 11.1 cm/sec). Mean transverse conduction velocity (TCV) was greater in LVH compared with control (20.5 ± 4.7 cm/sec vs 25.4 ± 8.1 cm/sec), but there was no significance in the trend as a function of HBR. The anisotropic ratio (LCV/TCV) significantly declined as HBR increased. The time constant of the foot of the action potential was smaller in the transverse compared with the longitudinal dimension. There was no influence of hypertrophy. Conclusion: The decrease of LCV and reduction of the anisotropic conduction ratio suggest remodeling of the tissue in LVH. The consequences for the generation of arrhythmias are discussed. [ABSTRACT FROM AUTHOR]

Natriuretic Peptide System in AF. Introduction: Circulating cardiac natriuretic peptides play an important role in maintaining volume homeostasis, especially during conditions affecting hemodynamics. During atrial fibrillation (AF), levels of plasma atrial natriuretic peptide (ANP) becomes elevated. The aim of this study was to gather Information about gene expression of the natriuretic peptide system on the atrial level in patients with AF. Methods and Results: Right atrial appendages of 36 patients with either paroxysmal or persistent AF were compared with 36 case matched controls in sinus rhythm for mRNA expression of pros atrial natriuretic peptide (pro-ANP), pro-brain natriuretic peptide (pro-BNP), and their natriuretic peptide receptor type-A (NPR-A). We investigated patients without (n = 36) and with (n = 36) valvular disease. Persistent Al was associated with higher mRNA expression of pro-BNP (+66%, P = 0.04, in patients without valvular disease, and +69%, p < 0.01, in patients with valvular disease) and lower mRNA expression of NPR-A (58%, P = 0.02, in patients without valvular disease, and -62%, P < 0.01, in patients with valvular disease). The mRNA content of pro-ANP was only increased in patients with valvular disease (+12%, P = 0.03). No changes were observed in patients with paroxysmal AF. Conclusion: This study demonstrates that persistent, but not paroxysmal, AF induces alterations in gene expression of pro-BNP and NPR-A on the atrial level. Although AF generally is associated with an Increase of plasma ANP level, a change In mRNA content of pro-ANP Is only observed in the presence of concomitant valvular disease and is of minor magnitude. [ABSTRACT FROM AUTHOR]

Introduction: AV nodal reentrant tachycardia (AVNRT) is not always reproducibly inducible. The purpose of this study was to determine the mechanisms responsible for the lack of reproducible induction of AVNRT. Methods and Results: The induction of AVNRT was assessed with atrial burst pacing, and with atrial and ventricular programmed stimulation, each with one and two extrastimuli, in 103 patients with AVNRT. The stimulation protocol was repeated 10 times in the baseline state, during isoproterenol infusion, and after atropine administration, or until AVNRT was induced in 7 of 10 attempts. The mechanisms responsible for < 7 of 10 inductions were classified as: (1) the inability to achieve critical AH prolongation; (2) fast pathway block; and (3) slow pathway block. The induction endpoint was achieved in 90 patients: 55 in the baseline state, 34 during isoproterenol infusion, and 1 after atropine. The mechanism of noninducibility in the baseline state (n = 48) was the inability to achieve a critical AH interval in 20%, fast pathway block in 49%, and slow pathway block in 31% (P = 0.02). During isoproterenol ad-ministration (n = 14) and after atropine administration (n = 13), the three mechanisms were equally responsible for nonreproducible induction of AVNRT. Conclusions: The induction of AVNRT is poorly reproducible in approximately 10% of patients. In the baseline state, the most common reason for the inability to reproducibly induce AVNRT is fast pathway block. In the presence of isoproterenol or atropine, each of the three mechanisms was equally responsible for noninducibility of AVNRT. [ABSTRACT FROM AUTHOR]

Background: A 53-year-old male with heart failure secondary to anterior wall myocardial infarction treated with cardiac resynchronization-defibrillator (CRT-D) device presented with ventricular arrhythmia: repetitive incessant slow ventricular tachycardias (VT) below the CRT-D detection zone, accelerated ventricular rhythm, and numerous premature ventricular ectopic beats (ExV), resulting in loss of biventricular pacing.Methods and Results: Nonsustained monomorphic VT (nsVT) and ExV were observed in an electrocardiogram under biventricular stimulation. During noninvasive CRT-D programming, ventricular bigeminy reproducibly recurred only at right ventricular (RV) pacing and its morphology was almost identical to the stimulated beats. The left ventricular (LV) pacing failed to induce ventricular ectopy or tachycardia.Conclusions: This unusual case shows a rare phenomenon of late proarrhythmic effect due to the RV lead pacing-a new finding reported only in a few publications. Here we present our approach to CRT programming that suppressed the clinical arrhythmia without the need of catheter ablation and achieving the high biventricular pacing capture rate along with optimal hemodynamic CRT-D performance. [ABSTRACT FROM AUTHOR]

Atrial Fibrillation (AF) is the most commonly described cardiac arrhythmia found in the general population and can lead to adverse outcomes. Its onset and maintenance requires the presence of an arrhythmogenic substrate that predisposes the patient for risk of these types of arrhythmias and the occurrence of a trigger event. A major characteristic of AF-related structural remodelling is atrial fibrosis, a process closely related to inflammation. Autoimmune rheumatic diseases constitute systemic inflammatory disorders that can also present with cardiovascular manifestations, including a high incidence of AF, thus supporting the idea of a link between AF and inflammation. A vicious cycle exists in which inflammation leads to a higher prevalence of structural cardiovascular disease, which in turn leads to more inflammation and AF; in fact, inflammation is known to affect signalling pathways that lead to the development of AF. Therapy must first target systemic inflammation, since decreasing the inflammatory burden has consistently shown to positively ameliorate the prognosis. When this approach is not sufficient, rhythm or, when not feasible, rate control is indicated in addition to anticoagulant therapy. As far as the rhythm control strategy is concerned, antiarrhythmic drugs and/or catheter ablation should be considered. New mapping techniques allowing the characterization of the arrhythmic substrate have opened new perspectives and may help in the treatment of AF in these patients, since atrial tissue is the target of inflammation-induced arrhythmic alterations. In cases where the natural history of the arrhythmia itself is more advanced, in order to minimize the impact of AF on cardiac function as well as quality of life, a device-based therapy, including an "ablate and pace" approach could be adopted., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Several studies have shown the beneficial effect of renal denervation (RDN) in the treatment of ventricular arrhythmia, especially in the setting of heart failure (HF). However, the underlying mechanism of antiarrhythmic effect of RDN is unknown. Arrhythmogenic cardiac alternans, particularly spatially discordant repolarization alternans, characterized by simultaneous prolongation and shortening of action potential duration (APD) in different myocardial regions, is central to the genesis of ventricular fibrillation in HF. Whether RDN decreases the susceptibility to arrhythmogenic cardiac alternans in HF has never been addressed before. The authors used a rat model of post-myocardial infarction HF and dual voltage-calcium optical mapping to investigate whether RDN could attenuate arrhythmogenic cardiac alternans that predisposes to ventricular arrhythmias, as well as the hemodynamic effect of RDN in HF. The HF rats had increased body weights, dilated hearts, and lower blood pressure. The HF rats also had longer ventricular APDs and a delay in the decay of the calcium transient, typical electrophysiological features of human HF. Susceptibility to calcium transient alternans, APD alternans, and spatially discordant APD alternans was increased in the HF hearts. RDN significantly attenuated a delay in the decay of the calcium transient, calcium transient and APD alternans, and importantly, the discordant APD alternans, and thereby decreased the incidence of induced ventricular arrhythmia in HF. RDN did not further decrease blood pressure in HF rats. In conclusion, RDN improves calcium cycling and prevents spatially discordant APD alternans and ventricular arrhythmia in HF. RDN does not aggravate hemodynamics in HF.

Background: Andersen-Tawil syndrome (ATS1)–associated ventricular arrhythmias are initiated by frequent, hypokalemia-exacerbated, triggered activity. Previous ex vivo studies in drug-induced Andersen-Tawil syndrome (DI-ATS1) models have proposed that arrhythmia propensity in DI-ATS1 derives from cytosolic Ca2+ ([Ca2+]i) accumulation leading to increased triggered activity. Objective: The purpose of this study was to test the hypothesis that elevated [Ca2+]i with concomitant APD prolongation, rather than APD dispersion, underlies arrhythmia propensity during DI-ATS1. Methods: DI-ATS1 was induced in isolated guinea pig ventricles by perfusion of 2 mM KCl Tyrode solution containing 10 μM BaCl2. APD and [Ca2+]i from the anterior epicardium were quantified by ratiometric optical voltage (di-4-ANEPPS) or Ca2+ (Indo-1) mapping during right ventricular pacing with or without the ATP-sensitive potassium channel opener pinacidil (15 μM). Results: APD gradients under all conditions were insufficient for arrhythmia induction by programmed stimulation. However, 38% of DI-ATS1 preparations experienced ventricular tachycardias (VTs), and all preparations experienced a high incidence of premature ventricular complexes (PVCs). Pinacidil decreased APD and APD dispersion and reduced VTs (to 6%), and PVC frequency (by 79.5%). However, PVC frequency remained significantly greater relative to control (0.5% ± 0.3% of DI-ATS1). Importantly, increased arrhythmia propensity during DI-ATS1 was associated with diastolic [Ca2+]i accumulation and increased [Ca2+]i transient amplitudes. Pinacidil partially attenuated the former but did not alter the latter. Conclusion: The study data suggest that arrhythmias during DI-ATS1 may be a result of triggered activity secondary to prolonged APD and altered [Ca2+]i cycling and less likely dependent on large epicardial APD gradients forming the substrate for reentry. Therefore, therapies aimed at reducing [Ca2+]i rather than APD gradients may prove effective in treatment of ATS1. [Copyright &y& Elsevier]