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Background: The use of intracardiac electrograms to guide atrial fibrillation (AF) ablation has yielded conflicting results., Objectives: The authors evaluated the usefulness of spatiotemporal dispersion, a visually recognizable electric footprint of AF drivers, for the ablation of all forms of AF., Methods: The authors prospectively enrolled 105 patients admitted for AF ablation. AF was sequentially mapped in both atria with a 20-pole PentaRay catheter. The authors tagged and ablated only regions displaying electrogram dispersion during AF. Results were compared to a validation set in which a conventional ablation approach was used (pulmonary vein isolation/stepwise approach). To establish the mechanism underlying spatiotemporal dispersion of AF electrograms, the authors conducted realistic numerical simulations of AF drivers in a 2-dimensional model and optical mapping of ovine atrial scar-related AF., Results: Ablation at dispersion areas terminated AF in 95% of the 105 patients. After ablation of 17 ± 10% of the left atrial surface and 18 months of follow-up, the atrial arrhythmia recurrence rate was 15% after 1.4 ± 0.5 procedures per patient versus 41% in the validation set after 1.5 ± 0.5 procedures per patient (arrhythmia free-survival: 85% vs. 59%; log-rank p < 0.001). Compared with the validation set, radiofrequency times (49 ± 21 min vs. 85 ± 34.5 min; p = 0.001) and procedure times (168 ± 42 min vs. 230 ± 67 min; p < 0.0001) were shorter. In simulations and optical mapping experiments, virtual PentaRay recordings demonstrated that electrogram dispersion is mostly recorded in the vicinity of a driver., Conclusions: The clustering of intracardiac electrograms exhibiting spatiotemporal dispersion is indicative of AF drivers. Their ablation allows for a nonextensive and patient-tailored approach to AF ablation. (Substrate Ablation Guided by High Density Mapping in Atrial Fibrillation [SUBSTRATE HD]; NCT02093949)., (Copyright © 2017 American College of Cardiology Foundation. All rights reserved.)

Objectives: This study describes 5-year follow-up results of catheter ablation for atrial fibrillation (AF)., Background: Long-term efficacy following catheter ablation of AF remains unknown., Methods: A total of 100 patients (86 men, 14 women), age 55.7 ± 9.6 years, referred to our center for a first AF ablation (63% paroxysmal; 3.5 ± 1.4 prior ineffective antiarrhythmic agents) were followed for 5 years. Complete success was defined as absence of any AF or atrial tachycardia recurrence (clinical or by 24-h Holter monitoring) lasting ≥ 30 s., Results: Arrhythmia-free survival rates after a single catheter ablation procedure were 40%, 37%, and 29% at 1, 2, and 5 years, respectively, with most recurrences over the first 6 months. Patients with long-standing persistent AF experienced a higher recurrence rate than those with paroxysmal or persistent forms (hazard ratio [HR]: 1.9, 95% confidence interval [CI]: 1.0 to 3.5; p = 0.0462). In all, 175 procedures were performed, with a median of 2 per patient. Arrhythmia-free survival following the last catheter ablation procedure was 87%, 81%, and 63% at 1, 2, and 5 years, respectively. Valvular heart disease (HR: 6.0, 95% CI: 2.0 to 17.6; p = 0.0012) and nonischemic dilated cardiomyopathy (HR: 34.0, 95% CI: 6.3 to 182.1; p < 0.0001) independently predicted recurrences. Major complications (cardiac tamponade requiring drainage) occurred in 3 patients (3%)., Conclusions: In selected patients with AF, a catheter ablation strategy with repeat intervention as necessary provides acceptable long-term relief. Although most recurrences transpire over the first 6 to 12 months, a slow but steady decline in arrhythmia-free survival is noted thereafter., (Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: The purpose of this study was to determine whether the speed of response to clopidogrel loading predicts the final degree of response., Background: Fast inhibition of platelet aggregation is important in the setting of acute coronary syndromes and percutaneous coronary intervention, but its association with the final degree of inhibition is not well established., Methods: We performed a post hoc analysis of the ALBION study; early kinetic profiles of adenosine diphosphate 20 micromol/l maximal platelet aggregation (MPA) and DeltaMPA (with baseline sample as reference) were studied at 8 time points within the 24 h after clopidogrel loading (300, 600, or 900 mg) in non-ST-segment elevation acute coronary syndrome patients. Low response was defined as DeltaMPA <10% over the first 24 h, fast response as DeltaMPA > or =10% at 1 h or before loading (the others being slow responders), and high post-treatment platelet reactivity as MPA > or =56.56% (fourth quartile). Inflammatory markers (PAC-1 and P-selectin) and vasodilator-stimulated phosphoprotein (VASP) were also evaluated according to onset of action., Results: Fifty-five percent of patients were slow responders. Noncurrent smoking and body mass index > or =25 kg/m(2) were associated with slower and lower responses. High post-treatment platelet reactivity was more frequent in slow responders (28% vs. 14%, p < 0.0001). There was a clopidogrel dose-effect relationship on DeltaMPA, with a trend toward faster onset of platelet inhibition in the 900-mg loading dose group. Slow responders had a slower and lower decrease in PAC-1 and P-selectin and higher VASP index at 6 h (76.5% vs. 66.4%, p = 0.019) and 24 h (70.3% vs. 61.5%, p = 0.049)., Conclusions: Slow response to clopidogrel, within the first hour of administration, is a reliable marker of low response at 24 h and high post-treatment platelet reactivity., (Copyright (c) 2010 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: This study evaluated the role of pre-procedural clinical variables to predict procedural and clinical outcomes of catheter ablation in patients with long-lasting persistent atrial fibrillation (AF)., Background: Catheter ablation of persistent AF remains a challenging task., Methods: Catheter ablation was performed in 90 patients (76 men, age 57 +/- 11 years) with long-lasting persistent AF. The history of AF, echocardiographic parameters, presence of structural heart disease, and surface electrocardiogram (ECG) AF cycle length (CL) were assessed before ablation and analyzed with respect to procedural termination and clinical outcome. Mean follow-up was 28 +/- 4 months., Results: Persistent AF was terminated in 76 of 90 patients (84%) by ablation. The duration of continuous AF was shorter (p < 0.0001), the surface ECG AFCL was longer (p < 0.0001), and the left atrium was smaller (p < 0.01) in patients in whom AF was terminated by catheter ablation. The surface ECG AFCL was the only independent predictor of AF termination (p < 0.01). Maintenance of sinus rhythm was associated with a shorter duration of continuous AF (p < 0.0001), a longer surface ECG AFCL (p < 0.001), and a smaller left atrium (p < 0.05) compared with those with recurrent arrhythmia. In multivariate analysis, the surface ECG AFCL and the AF duration predicted clinical success of persistent AF ablation (p < 0.01 and p < 0.05, respectively)., Conclusions: The surface ECG AFCL is a clinically useful pre-ablation tool for predicting patients in whom sinus rhythm can be restored by catheter ablation. The duration of continuous AF and the surface ECG AFCL are predictive of maintenance of sinus rhythm., (2009 by the American College of Cardiology Foundation)

Objectives: This multicenter study sought to evaluate the long-term follow-up of patients ablated for idiopathic ventricular fibrillation (VF)., Background: Catheter ablation of idiopathic VF that targets ventricular premature beat (VPB) triggers has been shown to prevent VF recurrences on short-term follow-up., Methods: From January 2000, 38 consecutive patients from 6 different centers underwent ablation of primary idiopathic VF initiated by short coupled VPB. All patients had experienced at least 1 documented VF, with 87% having experienced > or =2 VF episodes in the preceding year. Catheter ablation was guided by activation mapping of VPBs or pace mapping during sinus rhythm., Results: There were 38 patients (21 men) age 42 +/- 13 years, refractory to a median of 2 antiarrhythmic drugs. Triggering VPBs originated from the right (n = 16), the left (n = 14), or both (n = 3) Purkinje systems and from the myocardium (n = 5). During a median post-procedural follow-up of 63 months, 7 (18%) of 38 patients experienced VF recurrence at a median of 4 months. Five of these 7 patients underwent repeat ablation without VF recurrence. Survival free of VF was predicted only by transient bundle-branch block in the originating ventricle during the electrophysiological study (p < 0.0001). The number of significant events (confirmed VF or aborted sudden death) was reduced from 4 (interquartile range 3 to 9) before to 0 (interquartile range 0 to 4) after ablation (p = 0.01)., Conclusions: Ablation for idiopathic VF that targets short coupled VPB triggers is associated with a long-term freedom from VF recurrence.

Objectives: This study sought to characterize left atrial (LA) sinus rhythm electrogram (EGM) patterns and their relationship to parasympathetic responses during atrial fibrillation (AF) ablation., Background: The mechanistic basis of fractionated LA EGMs in patients with paroxysmal AF is not well understood., Methods: We analyzed 1,662 LA ablation sites from 30 patients who underwent catheter ablation for paroxysmal AF. Pre-ablation EGM characteristics (number of deflections, amplitude, and duration) were measured in sinus rhythm. Parasympathetic responses during radiofrequency application (increase of atrial-His interval by > or =10 ms or decrease of sinus rate by > or =20%) were assessed at all sites. We also prospectively studied the effect of adenosine, a pharmacological agent mimicking acetylcholine signaling in myocytes, on LA EGMs. Finally, we performed mathematical simulations of atrial tissue to delineate possible mechanisms of fractionated EGMs in sinus rhythm., Results: A specific pattern of pre-ablation sinus rhythm EGM (deflections > or =4, amplitude > or =0.7 mV, and duration > or =40 ms) was strongly associated with parasympathetic responses (sensitivity 72%, specificity 91%). The sites associated with these responses were found to be located mainly in the posterior wall of the LA. Adenosine administration and mathematical simulation of the effect of acetylcholine were able to reproduce a similar EGM pattern., Conclusions: Parasympathetic activation during AF ablation is associated with the presence of pre-ablation high-amplitude fractionated EGMs in sinus rhythm. Local acetylcholine release could potentially explain this phenomenon.

Objectives: We sought to compare the antiplatelet effects of three clopidogrel loading doses (LDs)., Background: Administration of a 300-mg clopidogrel LD is beneficial in situations requiring rapid platelet inhibition. Whether higher LDs can provide further benefits remains unknown., Methods: Patients (n = 103) with non-ST-segment elevation acute coronary syndromes were randomized to receive a 300-mg, 600-mg, or 900-mg clopidogrel LD, given on top of other standard therapy (including acetylsalicylic acid). The main outcome measure was inhibition of adenosine diphosphate-induced inhibition of platelet aggregation (IPA); inhibition of platelet activation, inflammatory markers, troponin I release, and major adverse cardiac events also were evaluated; all measures were blindly evaluated., Results: Compared with the 300-mg LD, greater doses were associated with significantly greater platelet inhibition, with dose-effect relationships observed for onset of action, maximal plateau, 24-h areas under the curves of IPA, and rates of low IPA (<10% at 6 h), using 20 micromol/l major adverse cardiac events. A significant dose-response was also observed for the vasodilator-stimulated phosphoprotein index, a measure of P2Y(12) receptor inhibition. Similar but nonsignificant trends were observed for troponin release and major adverse cardiac events. Bleeding rates were similar in each group., Conclusions: In low-to-moderate risk patients with non-ST-elevation acute coronary syndromes, clopidogrel LDs >300 mg provide a faster onset of action, a higher IPA plateau, and greater reductions in platelet activation during the first 24 h. A 900-mg LD may induce a greater antiplatelet effect than 600 mg, when compared with the standard 300-mg regimen. These findings require further clinical confirmation.