R ecent reports of asymptomatic cerebral lesions imaged with diffusion weighted MRI (DWI) after catheter ablation of atrial fibrillation have raised concerns about the safety of this procedure. [1][2][3][4][5] It has been speculated that these DWI lesions may be the result of cerebral microembolization, and that they could be a marker for procedure-related clinical stroke risk. 6 In addition, some speculate that the asymptomatic cerebral DWI lesions may, in fact, be associated with subtle abnormalities discernable with neuropsychiatric testing. 7,8 It has been established that thrombus, gas bubbles, and particulate debris (coagulum) can be introduced or produced with left atrial catheterization and catheter ablation in this chamber.9 New data are available on catheter ablation-related subclinical DWI lesions, often seen as punctate hyperintensities, from recent studies. However, the link between the size and characteristics of the emboli, produced with left atrial catheter ablation procedures has not been correlated to clinical stroke or subclinical DWI lesions. Clinical Perspective on p 30Considerable differences have been reported in typical lesion dimensions seen on DWI between various clinical stroke cohorts and patients with asymptomatic cerebral lesions detected on DWI after left atrial catheter ablation. There is a lack of causal data for any of the lesion types. The purpose of this canine study was to elucidate the characteristics of emboli capable of creating the DWI punctate hyperintensities seen in the clinical setting after left atrial catheter ablation procedures. We sought to differentiate the effects of embolizing pure gas microbubbles versus microparticles of smaller and larger size because smaller particles and gas microbubbles might be more likely to occlude flow in terminal cerebral vessels, and produce DWI lesions typical to those seen in asymptomatic patients after atrial fibrillation ablation. MethodsAll animal procedures were approved by and carried out in compliance with a preclinical research protocol by the Institutional Animal Care and Use Committee of the Medtronic Physiological Research Laboratories. General animal husbandry and care was supervised by a veterinary staff in accordance with the guidelines in Background-Asymptomatic cerebral lesions have been observed on diffusion weighted MRI (DWI) scans shortly after catheter ablation of atrial fibrillation, but the pathogenesis of these lesions is incompletely understood. Methods and Results-Twelve dogs underwent selective catheterization of the internal carotid or vertebral arteries. Either a microbubbled mixture of air (1.0-4.0 mL), blood, contrast, and saline (n=5), or heat-dried pulverized blood (particle size <600 μm) mixed with saline and contrast (n=6) was injected. One sham control experiment was performed. MRI scans were performed preinjection, and at 1, 2, and 4 days postinjection. Neurological tests were performed daily. Gross pathology and histopathology were performed on the brains after being euthanized on day 4. Three ...

Objective-To compare the defibrillation eYcacy of a novel lead system placed in the middle cardiac vein with a conventional non-thoracotomy lead system. Methods-In eight pigs (weighing 35-71 kg), an electrode was advanced transvenously to the right ventricular apex (RV), with the proximal electrode in the superior caval vein (SCV). Middle cardiac vein (MCV) angiography was used to delineate the anatomy before a three electrode system (length 2 × 25 mm + 1 × 50 mm) was positioned in the vein. An active housing (AH) electrode was implanted in the left pectoral region. Ventricular fibrillation was induced and biphasic shocks were delivered by an external defibrillator. The defibrillation threshold was measured and the electrode configurations randomised to: RV→AH, RV+MCV→AH, MCV→AH, and RV→SCV+AH. Results-For these configurations, mean (SD) defibrillation thresholds were 27.3 (9.6) J, 11.9 (2.9) J, 15.2 (4.3) J, and 21.8 (9.3) J, respectively. Both electrode configurations incorporating the MCV had defibrillation thresholds that were significantly less than those observed with the RV→AH (p < 0.001) and RV→SCV+AH (p < 0.05) configurations. Necropsy dissection showed that the MCV drained into the coronary sinus at a location close to its orifice (mean distance = 2.7 (2.2) mm). The MCV bifurcated into two main branches that drained the right and left ventricles, the left branch being the dominant vessel in the majority (6/7) of cases. Conclusions-Placement of specialised defibrillation electrodes within the middle cardiac vein provides more eVective defibrillation than a conventional tight ventricular lead. (Heart 2000;84:425-430)

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Defibrillation in the middle cardiac vein (MCV) has been shown to reduce ventricular defibrillation thresholds (DFTs). Low amplitude auxiliary shock (AS) from an electrode sutured to the left ventricle at thoracotomy have also been shown to reduce DFT if delivered immediately prior to a biphasic shock (between the ventricular RV and superior vena caval (SVC) electrodes). This study investigates the impact on DFT of an AS shock from a transvenously placed MCV lead system. A standard defibrillation electrode was positioned in the RV in eight anesthetized pigs (35-43 kg). A 50 x 1.8-mm electrode was inserted in the MCV through an 8 Fr angioplasty guide catheter. A 150-V (leading edge) monophasic AS was delivered (95 microF capacitor) from the MCV-->Can with three different pulse widths (3, 5, 7 ms). A primary biphasic shock (PS) (95 microF capacitor, phase 1: 44% tilt, 1.6-ms extension and phase 2: 2.5-ms fixed duration) was delivered from the RV-->Can +/- AS. The four configurations were randomized and DFTs (PS + AS) assessed using a modified binary search. Ventricular fibrillation (VF) was induced with 60 Hz AC followed 10 seconds later by the test shock. The DFTs were compared using repeated measures analysis of variance (ANOVA). All configurations incorporating AS produced significant (P < 0.05) reduction in the DFT compared to no AS (13.8 +/- 7.4 J). There was no difference in the efficacy of differing pulse widths (P > 0.05); 3 ms (11.0 +/- 5.4 J), 5 ms (11.5 +/- 6.0), and 7 ms (10.6 +/- 5.3 J). In conclusion, delivering an AS from a transvenous lead system deployed in the MCV reduces the DFT by 23% compared to a conventional RV-->Can shock alone.

Background-Pharmacological ventricular rate control is an acceptable atrial fibrillation (AF) therapy limited by systemic toxicity. We postulate that focal catheter-based drug delivery into the atrioventricular nodal (AVN) region may effectively control ventricular rate during AF without systemic toxicity. This study evaluated the effects of focally administered acetylcholine on AVN conduction and refractoriness during sinus rhythm and AF. Methods and Results-Canines (nϭ7) were anesthetized and instrumented to assess cardiac electrophysiology and blood pressure. A custom drug delivery catheter was implanted in the AVN region. Incremental doses of acetylcholine starting at 10 g/min were infused until complete AV block was achieved. Acetylcholine induced dose-dependent AV block. AF induction and electrophysiology measurements were performed during baseline and acetylcholine-induced first-degree and third-degree AV block. During AF, infusion of acetylcholine decreased ventricular rates from 182Ϯ32 to 77Ϯ28 and 28Ϯ8 bpm (first-degree and third-degree AV block, respectively; PϽ0.05). At the first-degree AV block dose, AVN effective refractory period increased from 186Ϯ37 to 282Ϯ33 ms, and Wenckebach cycle length increased from 271Ϯ29 to 378Ϯ58 ms (PϽ0.05). The first-degree AV block dose prolonged AV and AH intervals by 26% and 23% (PϽ0.05), whereas AA intervals and blood pressure remained unchanged, demonstrating a local effect. All effects were reversed 20 minutes after infusion was stopped. Conclusions-Focal acetylcholine delivery into the AVN increased AVN refractoriness and significantly decreased ventricular rate response during induced AF in a dose-related, reversible manner without systemic side effects. This may represent a novel therapy for AF whereby ventricular rate is controlled with the use of an implantable drug delivery system. (Circulation. 2006;113:2383-2390.)Key Words: acetylcholine Ⅲ catheters Ⅲ conduction Ⅲ pharmacology Ⅲ tachyarrhythmias C urrent clinical treatment options for arrhythmias include pharmacotherapy, ablation, and medical devices. Although these therapeutic approaches may have some role in the treatment of atrial fibrillation (AF), the successful management of this disease remains an unmet clinical need. Ideally, AF should be treated by a strategy of prevention and, if needed, conversion of the arrhythmia to a regular sinus rhythm. However, pharmacological therapies typically fail to prevent AF, particularly in patients with structural heart disease. Data from the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) trial and from other clinical trials suggest that AF management with the rhythm-control strategy offers no survival advantage over rate control and furthermore that rate control may be more advantageous (lower risk of adverse drug effects, lower number of hospitalizations, and lower healthcare burden). 1,2 For supraventricular tachyarrhythmias with fast ventricular response with origin of the focus in the atria, the most Editorial p 2374 Clinical Pers...