Electrophysiological characteristics of focal atrial tachycardia surrounding the aortic coronary cusps.

BACKGROUND: Catheter ablation of atrial tachycardia (AT) arising near the coronary cusps has been reported in limited numbers of patients. We investigated the electrophysiological characteristics of these ATs in 22 consecutive patients. METHODS AND RESULTS: This study included 22 patients (mean age ± SD, 53 ± 11 years; 86% female) with ATs arising near the aortic coronary cusps who underwent successful ablation. Activation mapping was performed during tachycardia to identify the earliest activation site. All patients achieved successful ablation through either a retrograde aortic (n=19) or a transseptal (n=3) approach. The successful ablation sites were located in the noncoronary cusp (NCC) (n=16), including 3 near the junction between the NCC and right coronary cusp. The remaining 6 cases were ablated from the left coronary cusp (LCC) (n=3) or the left atrium posterior to the LCC (n=3). For most tachycardias, there were distinctive P-wave morphological features recorded for each cusp location. Furthermore, analysis of the electrogram morphological features recorded during tachycardia at successful ablation sites revealed an atrial/ventricular (A/V) ratio >1 in 14 of 16 NCC ATs; the remaining 2, from the NCC near the junction with the right coronary cusp, showed an A/V ratio ≤ 1. At ablation sites in the LCC, the A/V ratio was <1 (4 of 6 patients) or 1 (remaining 2 patients). During a follow-up duration of 30 ± 13 months, all patients were free of arrhythmias without antiarrhythmic drugs. CONCLUSIONS: ATs surrounding the aortic coronary cusps can be safely and effectively ablated, with good long-term outcomes. In addition to the P-wave morphological features, the A/V ratio of the local electrogram recording during tachycardia facilitated the localization of successful sites.

Spontaneously alternating forms of the atrioventricular node reentrant tachycardia.

We present a case of atrioventricular node reentrant tachycardia that displays spontaneously alternating antegrade and retrograde conduction via 1:2 manners.

Inducibility of atrial fibrillation in the absence of atrial fibrillation: what does it mean to be normal?

BACKGROUND: While inducibility of atrial fibrillation (AF) is often used as an endpoint for radiofrequency ablation of AF, little is known regarding inducibility among normals. We therefore evaluated the inducibility of AF with rapid atrial pacing in patients without a clinical history of AF after catheter ablation of supraventricular tachycardia (SVT). METHODS: We prospectively evaluated 86 patients with no history of AF who were referred for catheter ablation of SVT. After successful ablation, two different rapid atrial pacing protocols for induction of AF were tested. First, AF induction was attempted by 5-second bursts of atrial pacing from the coronary sinus ostium (CSO) at three different cycle lengths (CLs). Next, decremental pacing was performed from the CSO starting at a CL of 250 ms to the loss of 1:1 atrial capture. This protocol was repeated 3 times for each subject. RESULTS: Three of the subjects (3.5%) enrolled had inducible AF with the first pacing protocol. However, with the second protocol, AF was inducible in 22 patients (25.6%), including sustained AF in 16 patients (18.6%). There were significant differences in the inducibility of AF between the two atrial pacing protocols. Additionally, with the second pacing protocol, patients with a loss of 1:1 atrial capture at CL <180 ms were more easily inducible for AF (21/63 vs. 1/23; P = .006). CONCLUSION: Using a specific, decremental pacing protocol, 26% of patients without a history of AF had inducible AF. These findings suggest that significant further investigation is needed to optimize the specificity of using AF induction as an endpoint for AF ablation.

Ethanol infusion in the vein of Marshall: Adjunctive effects during ablation of atrial fibrillation.

BACKGROUND: The vein of Marshall (VOM) is a left atrial (LA) vein that contains autonomic innervation and triggers of AF. Its location coincides with areas usually ablated during pulmonary vein (PV) antral isolation (PVAI). OBJECTIVE: This study sought to delineate the safety and ablative effects of ethanol infusion in the VOM during catheter ablation of atrial fibrillation (AF). METHODS: Patients undergoing PVAI (n = 14) gave consent for adjunctive VOM ethanol infusion. In 10 of 14 patients, the VOM was cannulated with an angioplasty wire and balloon. Echocardiographic contrast was injected in the VOM under echocardiographic monitoring. Two infusions of 100% ethanol (1 ml each) were delivered via the angioplasty balloon in the VOM. LA bipolar voltage maps were created before and after ethanol infusion. Radiofrequency ablation times required to isolate each PV and other procedural data were compared with those of 10 age-, sex-, AF type- and LA size-matched control subjects undergoing conventional PVAI. RESULTS: The VOM communicated with underlying myocardium, as shown by echocardiographic contrast passage into the LA. There were no acute complications related to VOM ethanol infusion, which led to the creation of a low-voltage area in the LA measuring 10.6 +/- 7.6 cm(2) and isolation of the left inferior PV in 4 of 10 patients. Radiofrequency ablation time required to achieve isolation of the left inferior PV was reduced (2.2 +/- 4 min vs. 11.4 +/- 10.3 min in control subjects, P <.05). CONCLUSION: VOM ethanol infusion is safe in humans, decreases radiofrequency ablation time in the left inferior PV, and may have a role as an adjunct to PVAI.

The angiotensin II type I receptor-associated protein, ATRAP, is a transmembrane protein and a modulator of angiotensin II signaling.

Our group identified angiotensin II type 1 (AT1) receptor-associated protein (ATRAP) in a yeast two-hybrid screen for proteins that bind to the carboxyl-terminal cytoplasmic domain of the AT1. In this work, we characterize ATRAP as a transmembrane protein localized in intracellular trafficking vesicles and plasma membrane that functions as a modulator of angiotensin II-induced signal transduction. ATRAP contains three hydrophobic domains at the amino-terminal end of the protein, encompassing the amino acid residues 14-36, 55-77, and 88-108 and a hydrophilic cytoplasmic carboxyl-terminal tail from residues 109-161. Endogenous and transfected ATRAP cDNA shows a particulate distribution; electron microscopy reveals the presence of ATRAP in prominent perinuclear vesicular membranes; and colocalization analysis by immunofluorescence shows that ATRAP colocalizes in an intracellular vesicular compartment corresponding to endoplasmic reticulum, Golgi, and endocytic vesicles. Real-time tracking of ATRAP vesicles shows constitutive translocation toward the plasma membrane. Using epitope-tagged forms of ATRAP at either the amino or carboxyl end of the molecule, we determined the orientation of the amino end as being outside the cell. Mutant forms of ATRAP lacking the carboxyl end are unable to bind to the AT1 receptor, leading to the formation of prominent perinuclear vesicle clusters. Functional analysis of the effects of ATRAP on angiotensin II-induced AT1 receptor signaling reveals a moderate decrease in the generation of inositol lipids, a marked decrease in the angiotensin II-stimulated transcriptional activity of the c-fos promoter luciferase reporter gene, and a decrease in cell proliferation.

Chronic infusion of beta-adrenoceptor antagonist and inverse agonists decreases elevated protein kinase A activity in transgenic mice with cardiac-specific overexpression of human beta 2-adrenoceptor.

Neutral antagonists and inverse agonists can produce different cellular responses in some systems. The effects of chronic (14-day) infusion of three ligands, ICI-118,551, carvedilol, and alprenolol were examined in cardiac tissue from wild-type and transgenic mice with cardiac-specific overexpression of the human beta2-adrenoceptor. These ligands vary in their negative efficacy at the human beta2-adrenoceptor, with two (ICI-118,551 and carvedilol) behaving as inverse agonists and one (alprenolol) behaving as a neutral antagonist. Cardiac tissue from the transgenic mice exhibited elevated levels of protein kinase A activity and G protein receptor kinase-2. Fourteen-day infusions of the three ligands lowered the elevated levels of protein kinase A activity of the transgenic hearts to control levels. Alprenolol and carvedilol also decreased G protein receptor kinase-2 amounts to control levels. The left atria from transgenic mice exhibited an impaired inotropic response to histamine relative to responses of wild-type mice atria. Infusions of the inverse agonists and a neutral antagonist at the beta2-adrenoceptor significantly restored the impaired histamine response. Restoration of protein kinase A activity and the impaired histamine responses in the atria from transgenic mice can be observed following 14-day infusions of both a neutral antagonist and inverse agonists. The reversal of the effects of the transgene by both inverse agonists and a neutral antagonist suggests that agonist occupancy, and not spontaneous activity, of the beta2-adrenoceptor is producing the elevated protein kinase A activity and the impaired histamine response.