Glenn D. Young

Effect of Atrial Fibrillation on Atrial Thrombogenesis in Humans: Impact of Rate and Rhythm

OBJECTIVES We sought to assess the effect of atrial fibrillation (AF) on atrial thrombogenesis in humans by determining the impact of rate and rhythm. BACKGROUND Although AF is known to increase the risk of thromboembolic stroke from the left atrium (LA), the exact mechanisms remain poorly understood. METHODS We studied 55 patients with AF who underwent catheter ablation while in sinus rhythm; 20 patients were induced into AF, 20 patients were atrial paced at 150 beats/min, and 15 were control patients. Blood samples were taken from the LA, right atrium, and femoral vein at baseline and at 15 min in all 3 groups. Platelet activation (P-selectin) was measured by flow cytometry. Thrombin generation (thrombin-antithrombin [TAT] complex), endothelial dysfunction (asymmetric dimethylarginine [ADMA]), and platelet-derived inflammation (soluble CD40 ligand [sCD40L]) were measured using enzyme-linked immunosorbent assay. RESULTS Platelet activation increased significantly in both the AF (p < 0.001) and pacing (p < 0.05) groups, but decreased in control patients (p < 0.001). Thrombin generation increased specifically in the LA compared with the periphery in both the AF (p < 0.01) and pacing (p < 0.01) groups, but decreased in control patients (p < 0.001). With AF, ADMA (p < 0.01) and sCD40L (p < 0.001) levels increased significantly at all sites, but were unchanged with pacing (ADMA, p = 0.5; sCD40L, p = 0.8) or in control patients (ADMA, p = 0.6; sCD40L, p = 0.9). CONCLUSIONS Rapid atrial rates and AF in humans both result in increased platelet activation and thrombin generation. Prothrombotic activation occurs to a greater extent in the human LA compared with systemic circulation. AF additionally induces endothelial dysfunction and inflammation. These findings suggest that although rapid atrial rates increase the thrombogenic risk, AF may further potentiate this risk.

Electrical remodelling of the left and right atria due to rheumatic mitral stenosis

AIMS To characterize the atrial remodelling in mitral stenosis (MS). METHODS AND RESULTS Twenty-four patients with severe MS undergoing commissurotomy and 24 controls were studied. Electrophysiological evaluation was performed in 12 patients in each group by positioning multi-electrode catheters in both atria to determine the following: effective refractory period (ERP) at 10 sites at 600 and 450 ms; conduction time; conduction delay at the crista terminalis (CT); and vulnerability for atrial fibrillation (AF). P-wave duration (PWD) was determined on the surface ECG. In the remaining 12 patients in each group, electroanatomic maps of both atria were created to determine conduction velocity and identify regions of low voltage and electrical silence. Patients with MS had larger left atria (LA) (P < 0.0001); prolonged PWD (P = 0.0007); prolonged ERP in both LA (P < 0.0001) and right atria (RA) (P < 0.0001); reduced conduction velocity in the LA (P = 0.009) and RA (P < 0.0001); greater number (P < 0.0001) and duration (P< 0.0001) of bipoles along the CT with delayed conduction; lower atrial voltage in the LA (P < 0.0001) and RA (P < 0.0001); and more frequent electrical scar (P = 0.001) compared with controls. Five of twelve with MS and none of the controls developed AF with extra-stimulus (P = 0.02). CONCLUSION Atrial remodelling in MS is characterized by LA enlargement, loss of myocardium, and scarring associated with widespread and site-specific conduction abnormalities and no change or an increase in ERP. These abnormalities were associated with a heightened inducibility of AF.

Effect of Dietary n-3 Polyunsaturated Fatty Acids on the Inducibility of Ventricular Tachycardia in Patients With Ischemic Cardiomyopathy

Increased consumption of fish and/or fish oil was associated with decreased risk of sudden cardiac death (SCD). The study aim was to evaluate the antiarrhythmic effect of dietary fish oil on the inducibility of ventricular tachycardia (VT) at high risk of SCD. Patients with coronary artery disease undergoing defibrillator implantation were recruited if sustained monomorphic VT could be induced by programmed extra stimuli at 2 cycle lengths. After the initial study, 12 patients consumed 3 g/d of encapsulated fish oil for approximately 6 weeks before a repeated electrophysiologic study. To control for fluctuations in the inducibility of VT, an additional 14 patients with no dietary manipulation were also studied. Aggressiveness of stimulation required to induce VT was ranked from least aggressive to most aggressive based on cycle length and number of extra stimuli, with noninducibility ranked highest. At the repeated electrophysiologic study, in the fish-oil group, 42% had no inducible VT, 42% required more aggressive stimulation to induce VT, 8% required identical stimulation, and 8% required less stimulation compared with 7%, 36%, 36%, and 21% in the control group, respectively. Overall, there was a change to noninducible or less inducible VT in the fish-oil group, but no change in the control group (p = 0.003 and p = 0.65, respectively; Wilcoxons sign-rank test). In conclusion, dietary n-3 fatty acid supplementation decreased the inducibility of VT in patients at risk of SCD. These findings suggest that dietary fish oil can have an antiarrhythmic effect.

High-Density Mapping of Atrial Fibrillation in Humans: Relationship Between High-Frequency Activation and Electrogram Fractionation

Introduction: Sites of complex fractionated atrial electrograms (CFAE) and dominant frequency (DF) have been implicated in maintaining atrial fibrillation (AF); however, their relationship is poorly understood.

Effect of Dietary Fish Oil on Atrial Fibrillation After Cardiac Surgery

An open-label study reported that ingestion of a fish oil concentrate decreased the incidence of atrial fibrillation (AF) after coronary artery bypass grafting (CABG) surgery. However, a general cardiac surgery population involves valve and CABG surgeries. We undertook a double-blinded randomized controlled trial to examine the effectiveness of fish oil supplementation on the incidence of postsurgical AF after CABG and valve procedures. The primary end point was incidence of AF in the first 6 days after surgery. Two hundred patients were randomized to receive fish oil (providing 4.6 g/day of long-chain ω-3 fatty acids) or a control oil starting 3 weeks before surgery; 194 subjects completed the study, with 47 of 97 subjects in the control group and 36 of 97 subjects in the fish oil group developing AF (odds ratio 0.63, 95% confidence interval [CI] 0.35 to 1.11). There was a nonstatistically significant delay in time to onset of AF in the fish oil group (hazard ratio 0.66, 95% CI 0.43 to 1.01). There was a significant decrease in mean length of stay in the intensive care unit in the fish oil group (ratio of means 0.71, 95% CI 0.56 to 0.90). In conclusion, in a mixed cardiac surgery population, supplementation with dietary fish oil did not result in a significant decrease in the incidence of postsurgical AF. However, there was a significant decrease in time spent in the intensive care unit.

The Effect of Electrogram Duration on Quantification of Complex Fractionated Atrial Electrograms and Dominant Frequency

Introduction: Sites of complex fractionated atrial electrograms (CFAEs) and highest dominant frequency (DF) have been proposed as critical regions maintaining atrial fibrillation (AF). This study aimed to determine the minimum electrogram recording duration that accurately characterizes CFAE or DF sites for ablation without unduly lengthening the procedure.

Image integration using NavX fusion: Initial experience and validation

BACKGROUND Three-dimensional virtual anatomic navigation is increasingly used during mapping and ablation of complex arrhythmias. NavX Fusion software aims to mold the virtual anatomy to the patients computed tomography (CT) image; however, the accuracy and clinical usefulness of this system have not been reported. OBJECTIVE The purpose of this study was to assess the accuracy and describe the initial experience of CT image integration using NavX Fusion for atrial fibrillation ablation. METHODS This study consisted of 55 consecutive patients undergoing atrial fibrillation ablation using NavX Fusion navigation. Left atrial NavX geometries were compared to a corresponding CT for geometric match. Geometric match, expressed as the difference in millimeters between CT and NavX geometry, was calculated for the original geometry (GEO-1), field scaled and primary fused geometry (GEO-2), and final secondary fused geometry (GEO-3). Navigational accuracy was assessed by moving the catheter to 10 discrete anatomic sites and determining the distance between the catheter tip and the closest GEO-2, GEO-3, and CT surface. Fusion integration time and procedural and fluoroscopic durations were recorded to assess clinical usefulness. RESULTS GEO-1, GEO-2 and GEO-3 were associated with CT-GEO errors of 6.6+/-2.8 mm, 4.1+/-0.7 mm, 1.9+/-0.4 mm, respectively. Navigational accuracy was not significantly different for GEO-2, GEO-3, and CT at 3.4+/-1.6 mm to any surface. A significant (P < or =.001) inverse curvilinear relationship was present between case number and the time required for image integration (r(2) = 0.35) and the fluoroscopic time normalized for procedural duration (r(2) = 0.18). CONCLUSION Image integration using the NavX Fusion software is highly accurate and is associated with a progressive reduction in fluoroscopic time relative to procedural duration.

Long-term mechanical consequences of permanent right ventricular pacing: Effect of pacing site

Optimal Right Ventricular Pacing Introduction: Long‐term right ventricular apical (RVA) pacing has been associated with adverse effects on left ventricular systolic function; however, the comparative effects of right ventricular outflow tract (RVOT) pacing are unknown. Our aim was therefore to examine the long‐term effects of septal RVOT versus RVA pacing on left ventricular and atrial structure and function.

Time course of inflammation, myocardial injury, and prothrombotic response after radiofrequency catheter ablation for atrial fibrillation

Background—Inflammation has been linked to the genesis of stroke in atrial fibrillation (AF) and is implicated in early recurrent arrhythmia after AF ablation. We aimed to define the time course of inflammation, myocardial injury, and prothrombotic markers after radiofrequency ablation for AF and its relation to AF recurrence. Methods and Results—Ninety consecutive AF patients (53% paroxysmal) undergoing radiofrequency ablation were recruited. High-sensitivity C-reactive protein (hs-CRP), Troponin-T, creatine kinase-MB, fibrinogen, and D-Dimer concentrations were measured at baseline, at 1, 2, 3, 7 days, and at 1 month after ablation. AF recurrence was documented at 3 days and at 1, 3, and 6 months follow-up. Troponin-T and creatine kinase-MB peaked at day 1 after procedure (both P<0.05). Hs-CRP peaked at day 3 after procedure (P<0.05). Fibrinogen (P<0.05) and D-Dimer (P<0.05) concentrations were significantly elevated at 1 week after procedure. Ln hs-CRP elevation correlated with Ln Troponin-T and fibrinogen elevation. The extent of Ln hs-CRP, Ln Troponin-T, and fibrinogen elevation predicted early AF recurrence within 3 days after procedure (P<0.05, respectively), but not at 3 and 6 months. Conclusions—Patients undergoing radiofrequency ablation for AF exhibit an inflammatory response within 3 days. The extent of inflammatory response predicts early AF recurrence but not late recurrence. Prothrombotic markers are elevated at 1 week after ablation and may contribute to increased risk of early thrombotic events after AF ablation.

Relation between blood and atrial fatty acids in patients undergoing cardiac bypass surgery

BACKGROUND Studies relating cardiovascular outcomes to dietary or blood measures of various fatty acids rely on the implicit assumptions that dietary change results in changes in blood fatty acids that, in turn, alter cardiac fatty acids. Although dietary intakes of n-3 (omega-3), n-6 (omega-6), and trans fatty acids are reflected in their concentrations in blood, there are few human data on the relation between blood and cardiac concentrations of fatty acids. OBJECTIVE The objective was to explore relations between blood and myocardial n-3, n-6, trans, monosaturated, and saturated fatty acids over a range of community intakes to evaluate whether blood fatty acids are useful surrogate markers of their cardiac counterparts. DESIGN Patients undergoing on-pump coronary bypass surgery were recruited. Right atrial appendages and blood were collected at surgery for fatty acid analysis. RESULTS Atrial appendages and matching blood samples were collected from 61 patients. Highly significant correlations were identified between atrial and erythrocyte or plasma n-3 [eg, eicosapentaenoic acid (erythrocytes: r = 0.93, P < 0.0001; plasma: r = 0.87, P < 0.0001)], some n-6 [eg, arachidonic acid (erythrocytes: r = 0.45, P = 0.0003; plasma: r = 0.39, P = 0.002)], trans [eg, total trans 18:1 (erythrocytes: r = 0.89, P < 0.0001; plasma: r = 0.74, P < 0.0001)], and monounsaturated [eg, oleic acid (erythrocytes: r = 0.37, P = 0.003)] fatty acids. There were no statistical associations between blood and cardiac saturated fatty acids. CONCLUSION Erythrocyte- and plasma phospholipid-derived fatty acids can be used to estimate cardiac fatty acid status in humans.