Effect of Left Atrial Wall Thickness on Radiofrequency Ablation Success.

INTRODUCTION: Radiofrequency (RF) ablation in thicker regions of the left atrium (LA) may require increased ablation energy in order to achieve effective transmural lesions. Consequently, many cases of recurrent atrial fibrillation (AF) postablation may be due to thicker-than-normal atrial tissue. The aim of this study was to test the hypotheses that patients with recurrent AF have thicker tissue overall and that electrical reconnection is more likely in regions of thicker tissue. METHODS AND RESULTS: Retrospective analysis was performed on 86 CT images acquired preoperatively from a cohort of 119 patients who had undergone RF ablation for AF. Of these, 33 patients experienced recurrence of AF within 1 year of initial treatment and 29 returned for a repeat ablation. For each patient, LA wall thickness (LAWT) was measured from the images in 12 anatomical regions using custom software. Patients with recurrent AF had larger LAWT compared to successfully treated patients (1.6 ± 0.6 mm vs. 1.5 ± 0.5 mm, P \u3c 0.001) and reconnection was found to be at regions of thicker tissue (1.6 ± 0.6 mm, P = 0.038) compared to nonreconnected regions (1.5 ± 0.5 mm). The superior right posterior wall of the LA was significantly related to both recurrence (P = 0.048) and reconnection (P = 0.014). CONCLUSION: Increased LAWT has a small but significant effect on postablation recurrence and reconnection. Measures of LAWT may facilitate appropriate dosing of RF energy, but other factors will be critical in transmural lesion formation and ablation success

Design and Evaluation of a Catheter Contact-Force Controller for Cardiac Ablation Therapy.

GOAL: Maintaining a constant contact force (CF) of an ablation catheter during cardiac catheter ablation therapy is clinically challenging due to inherent myocardial motion, often resulting in poor ablation of arrhythmogenic substrates. To enable a prescribed contact force to be applied during ablation, a catheter contact force controller (CCFC) was developed. METHODS: The system includes a hand-held device attached to a commercial catheter and steerable sheath. A compact linear motor assembly attaches to an ablation catheter and autonomously controls its relative position within the shaft of the steerable sheath. A closed-loop control system is implemented within embedded electronics to enable real-time catheter-tissue contact force control. To evaluate the performance of the CCFC, a linear motion phantom was used to impose a series of physiological CF profiles; lesion CF was controlled at prescribed levels ranging from 15 to 40 g. RESULTS: For a prescribed CF of 25 g, the CCFC was able to regulate the CF with a root mean squared error of 3.7 ± 0.7 g. The ability of the CCFC to retract the catheter upon sudden changes in tissue motion, which may have caused tissue damage, was also demonstrated. Finally, the device was able to regulate the CF for a predetermined amount of time according to a force-time integral model. CONCLUSION: The developed CCFC is capable of regulating catheter-tissue CF in a laboratory setting that mimics clinical ablation therapy. SIGNIFICANCE: Catheter-tissue CF control promises to improve the precision and success of ablation lesion delivery

Eliminating the effects of motion during radiofrequency lesion delivery using a novel contact-force controller.

INTRODUCTION: Catheter-tissue contact force is a determinant of radiofrequency (RF) ablation lesion effectiveness. However, ablation on a beating heart is subject to force variability, making it difficult to optimally deliver consistently durable and transmural lesions. This work evaluates improvements in contact force stability and lesion reproducibility by using a catheter contact-force controller (CFC) during lesion delivery in vitro and in vivo. METHODS AND RESULTS: Using a sheath and force-sensing catheter, an experienced operator attempted to maintain a constant force of 20 g at targets within the atria and left ventricle of a pig manually and using the CFC; the average force and contact-force variation (CFV) achieved using each approach were compared. Ablation lesions (20 W, 30 seconds, 17 mL/min irrigation) were created in bovine tissue samples mounted on a platform programmed to reproduce clinically relevant motion. CFC-assisted lesions were delivered to stationary and moving tissue with forces of 5 to 35  g. Mimicking manual intervention, lesions were also delivered to moving tissue while the CFC was disabled. Resultant lesion volumes were compared using two-way analysis of variance. When using the CFC, the average force was within 1 g of the set level, with a CFV less than 5 g, during both in vitro and in vivo experiments. Reproducible and statistically identical (P = .82) lesion volumes proportional to the set force were achieved in both stationary and moving tissue when the CFC was used. CONCLUSIONS: CFC assistance maintains constant force in vivo and removes effect of motion on lesion volume during RF lesion delivery

How to diagnose the cause of sudden cardiac arrest

Sudden cardiac death or sudden cardiac arrest (SCA) is defined as natural death that occurs within an hour of the onset of acute symptoms or during sleep due to a primary cardiac cause. Most cases of SCA are attributable to coronary artery disease, with occult cardiomyopathy or inheritable arrhythmic syndromes accounting for a minority of SCA. Diagnosing the cause of SCA has potential implications for the patient and the family, and demands a comprehensive approach. This review summarizes the potential causes of SCA and outlines a systematic diagnostic approach to the SCA survivor. (Cardiol J 2011; 18, 2: 210-216

Progression to chronic atrial fibrillation after pacing: the Canadian Trial of Physiologic Pacing

AbstractOBJECTIVESThis study examined the effect of physiologic pacing on the development of chronic atrial fibrillation (CAF) in the Canadian Trial Of Physiologic Pacing (CTOPP).BACKGROUNDThe role of physiologic pacing to prevent CAF remains unclear. Small randomized studies have suggested a benefit for patients with sick sinus syndrome. No data from a large randomized trial are available.METHODSThe CTOPP randomized patients undergoing first pacemaker implant to ventricular-based or physiologic pacing (AAI or DDD). Patients who were prospectively found to have persistent atrial fibrillation (AF) lasting greater than or equal to one week were defined as having CAF. Kaplan-Meier plots for the development of CAF were compared by log-rank test. The effect of baseline variables on the benefit of physiologic pacing was evaluated by Cox proportional hazards modeling.RESULTSPhysiologic pacing reduced the development of CAF by 27.1%, from 3.84% per year to 2.8% per year (p = 0.016). Three clinical factors predicted the development of CAF: age ≥74 years (p = 0.057), sinoatrial (SA) node disease (p < 0.001) and prior AF (p < 0.001). Subgroup analysis demonstrated a trend for patients with no history of myocardial infarction or coronary disease (p = 0.09) as well as apparently normal left ventricular function (p = 0.11) to derive greatest benefit.CONCLUSIONSPhysiologic pacing reduces the annual rate of development of chronic AF in patients undergoing first pacemaker implant. Age ≥74 years, SA node disease and prior AF predicted the development of CAF. Patients with structurally normal hearts appear to derive greatest benefits

Effects of competition on pattern formation in the rock-paper-scissors game

We investigate the impact of cyclic competition on pattern formation in the rock-paper-scissors game. By separately considering random and prepared initial conditions, we observe a critical influence of the competition rate $p$ on the stability of spiral waves and on the emergence of biodiversity. In particular, while increasing values of $p$ promote biodiversity, they may act detrimental on spatial pattern formation. For random initial conditions, we observe a phase transition from biodiversity to an absorbing phase, whereby the critical value of mobility grows linearly with increasing values of $p$ on a log-log scale, but then saturates as $p$ becomes large. For prepared initial conditions, we observe the formation of single-armed spirals, but only for values of $p$ that are below a critical value. Once above, the spirals break up and form disordered spatial structures, mainly because of the percolation of vacant sites. Thus, there exists a critical value of the competition rate $p_{c}$ for stable single-armed spirals in finite populations. Importantly though, $p_{c}$ increases with increasing system size, because noise reinforces the disintegration of ordered patterns. In addition, we also find that $p_{c}$ increases with the mobility. These phenomena are reproduced by a deterministic model that is based on nonlinear partial differential equations. Our findings indicate that competition is vital for the sustenance of biodiversity and emergence of pattern formation in ecosystems governed by cyclical interactions.Comment: 7 two-column pages, 7 figures; accepted for publication in Physical Review

Edoxaban: an update on the new oral direct factor Xa inhibitor.

Edoxaban is a once-daily oral anticoagulant that rapidly and selectively inhibits factor Xa in a concentration-dependent manner. This review describes the extensive clinical development program of edoxaban, including phase III studies in patients with non-valvular atrial fibrillation (NVAF) and symptomatic venous thromboembolism (VTE). The ENGAGE AF-TIMI 48 study (N = 21,105; mean CHADS2 score 2.8) compared edoxaban 60 mg once daily (high-dose regimen) and edoxaban 30 mg once daily (low-dose regimen) with dose-adjusted warfarin [international normalized ratio (INR) 2.0-3.0] and found that both regimens were non-inferior to warfarin in the prevention of stroke and systemic embolism in patients with NVAF. Both edoxaban regimens also provided significant reductions in the risk of hemorrhagic stroke, cardiovascular mortality, major bleeding and intracranial bleeding. The Hokusai-VTE study (N = 8,292) in patients with symptomatic VTE had a flexible treatment duration of 3-12 months and found that following initial heparin, edoxaban 60 mg once daily was non-inferior to dose-adjusted warfarin (INR 2.0-3.0) for the prevention of recurrent VTE, and also had a significantly lower risk of bleeding events. Both studies randomized patients at moderate-to-high risk of thromboembolic events and were further designed to simulate routine clinical practice as much as possible, with edoxaban dose reduction (halving dose) at randomisation or during the study if required, a frequently monitored and well-controlled warfarin group, a well-monitored transition period at study end and a flexible treatment duration in Hokusai-VTE. Given the phase III results obtained, once-daily edoxaban may soon be a key addition to the range of antithrombotic treatment options

Ankyrin-B dysfunction predisposes to arrhythmogenic cardiomyopathy and is amenable to therapy

Arrhythmogenic cardiomyopathy (ACM) is an inherited arrhythmia syndrome characterized by severe structural and electrical cardiac phenotypes, including myocardial fibrofatty replacement and sudden cardiac death. Clinical management of ACM is largely palliative, owing to an absence of therapies that target its underlying pathophysiology, which stems partially from our limited insight into the condition. Following identification of deceased ACM probands possessing ANK2 rare variants and evidence of ankyrin-B loss of function on cardiac tissue analysis, an ANK2 mouse model was found to develop dramatic structural abnormalities reflective of human ACM, including biventricular dilation, reduced ejection fraction, cardiac fibrosis, and premature death. Desmosomal structure and function appeared preserved in diseased human and murine specimens in the presence of markedly abnormal \u3b2-catenin expression and patterning, leading to identification of a previously unknown interaction between ankyrin-B and \u3b2-catenin. A pharmacological activator of the WNT/\u3b2-catenin pathway, SB-216763, successfully prevented and partially reversed the murine ACM phenotypes. Our findings introduce what we believe to be a new pathway for ACM, a role of ankyrin-B in cardiac structure and signaling, a molecular link between ankyrin-B and \u3b2-catenin, and evidence for targeted activation of the WNT/\u3b2-catenin pathway as a potential treatment for this disease

Visualization of elusive structures using intracardiac echocardiography: Insights from electrophysiology

Electrophysiological mapping and ablation techniques are increasingly used to diagnose and treat many types of supraventricular and ventricular tachycardias. These procedures require an intimate knowledge of intracardiac anatomy and their use has led to a renewed interest in visualization of specific structures. This has required collaborative efforts from imaging as well as electrophysiology experts. Classical imaging techniques may be unable to visualize structures involved in arrhythmia mechanisms and therapy. Novel methods, such as intracardiac echocardiography and three-dimensional echocardiography, have been refined and these technological improvements have opened new perspectives for more effective and accurate imaging during electrophysiology procedures. Concurrently, visualization of these structures noticeably improved our ability to identify intracardiac structures. The aim of this review is to provide electrophysiologists with an overview of recent insights into the structure of the heart obtained with intracardiac echocardiography and to indicate to the echo-specialist which structures are potentially important for the electrophysiologist