Stéphane Garrigue

Spontaneous Initiation of Atrial Fibrillation by Ectopic Beats Originating in the Pulmonary Veins

BACKGROUND Atrial fibrillation, the most common sustained cardiac arrhythmia and a major cause of stroke, results from simultaneous reentrant wavelets. Its spontaneous initiation has not been studied. METHODS We studied 45 patients with frequent episodes of atrial fibrillation (mean [+/-SD] duration, 344+/-326 minutes per 24 hours) refractory to drug therapy. The spontaneous initiation of atrial fibrillation was mapped with the use of multielectrode catheters designed to record the earliest electrical activity preceding the onset of atrial fibrillation and associated atrial ectopic beats. The accuracy of the mapping was confirmed by the abrupt disappearance of triggering atrial ectopic beats after ablation with local radio-frequency energy. RESULTS A single point of origin of atrial ectopic beats was identified in 29 patients, two points of origin were identified in 9 patients, and three or four points of origin were identified in 7 patients, for a total of 69 ectopic foci. Three foci were in the right atrium, 1 in the posterior left atrium, and 65 (94 percent) in the pulmonary veins (31 in the left superior, 17 in the right superior, 11 in the left inferior, and 6 in the right inferior pulmonary vein). The earliest activation was found to have occurred 2 to 4 cm inside the veins, marked by a local depolarization preceding the atrial ectopic beats on the surface electrocardiogram by 106+/-24 msec. Atrial fibrillation was initiated by a sudden burst of rapid depolarizations (340 per minute). A local depolarization could also be recognized during sinus rhythm and abolished by radiofrequency ablation. During a follow-up period of 8+/-6 months after ablation, 28 patients (62 percent) had no recurrence of atrial fibrillation. CONCLUSIONS The pulmonary veins are an important source of ectopic beats, initiating frequent paroxysms of atrial fibrillation. These foci respond to treatment with radio-frequency ablation.

Long-term benefits of biventricular pacing in congestive heart failure : Results from the multisite stimulation in cardiomyopathy (MUSTIC) study

OBJECTIVES The main objective of this study was to assess if the benefits of biventricular (BiV) pacing observed during the crossover phase were sustained over 12 months. BACKGROUND MUltisite STimulation In Cardiomyopathies (MUSTIC) is a randomized controlled study intended to evaluate the effects of BiV pacing in patients with New York Heart Association (NYHA) class III heart failure and intraventricular conduction delay. METHODS Of 131 patients included, 42/67 in sinus rhythm (SR) and 33/64 in atrial fibrillation (AF) were followed up longitudinally at 9 and 12 months by 6-min walked distance, peak oxygen uptake (peak VO(2)), quality of life by the Minnesota score, NYHA class, echocardiography, and left ventricular ejection fraction by radionuclide technique. RESULTS At 12 months, all SR and 88% of AF patients were programmed to BiV pacing. Compared with baseline, the 6-min walked distance increased by 20% (SR) (p = 0.0001) and 17% (AF) (p = 0.004); the peak VO(2) by 11% (SR) and 9% (AF); quality of life improved by 36% (SR) (p = 0.0001) and 32% (AF) (p = 0.002); NYHA class improved by 25% (SR) (p = 0.0001) and 27% (AF) (p = 0.0001). The ejection fraction improved by 5% (SR) and 4% (AF). Mitral regurgitation decreased by 45% (SR) and 50% (AF). CONCLUSIONS The clinical benefits of BiV pacing appeared to be significantly maintained over a 12-month follow-up period.

Electrophysiological Breakthroughs From the Left Atrium to the Pulmonary Veins

Background—The extent of ostial ablation necessary to electrically disconnect the pulmonary vein (PV) myocardial extensions that initiate atrial fibrillation from the left atrium has not been determined. Methods and Results—Seventy patients underwent PV mapping with a circumferential 10-electrode catheter during sinus rhythm or left atrial pacing. After assessment of perimetric distribution and activation sequence of PV potentials, ostial ablation was performed at segments showing earliest activation, with the end point of PV disconnection. A total of 162 PVs (excluding right inferior PVs) were ablated. PV potentials were present at 60% to 88% of their perimeter, but PV muscle activation was always sequential from a segment with earliest activation (breakthrough). Radiofrequency (RF) application at this breakthrough eliminated all PV potentials in 34 PVs, whereas a secondary breakthrough required RF applications at separate segments in 77; in others, >2 segments were ablated. A median of 5, 6, and 4 bipoles from the circular catheter were targeted in the right superior, left superior, and inferior PVs, respectively, to achieve PV disconnection. Early recurrence of arrhythmia was observed in 31 patients as a result of new venous or atrial foci or recovery of previously targeted PVs, most related to a single recovered breakthrough that was reablated with local RF application. Conclusions—Although PV muscle covers a large extent of the PV perimeter, there are specific breakthroughs from the left atrium that allow ostial PV disconnection by use of partial perimetric ablation.

Electrophysiological End Point for Catheter Ablation of Atrial Fibrillation Initiated From Multiple Pulmonary Venous Foci

BACKGROUND The end point for catheter ablation of pulmonary vein (PV) foci initiating atrial fibrillation (AF) has not been determined. METHODS AND RESULTS Ninety patients underwent mapping during spontaneous or induced ectopy and/or AF initiation. Ostial PV ablation was performed by use of angiograms to precisely define targeted sites. Success defined by elimination of AF without drugs was correlated with the procedural end point of the abolition of distal PV potentials. A total of 197 arrhythmogenic PV foci (97%)-single in 31% and multiple in 69%-and 6 atrial foci were identified. A discrete radiofrequency (RF) application eliminated the PV potentials in 9 PV foci, whereas 2 foci from the same PV required RF applications at separate sites in 19 cases. In others, a wider region was targeted with progressive elimination of ectopy. In 49 patients, multiple sessions were necessary owing to recurrent or new ectopy. The clinical success rates were 93%, 73%, and 55% in patients with 1, 2, and > or =3 arrhythmogenic PV foci. Recovery of local PV potential and the inability to abolish it were significantly associated with AF recurrences (90% success rate with versus 55% without PV potential abolition). PV stenosis was noted acutely in 5 of 6 cases, remained unchanged at restudy, and was associated with RF power >45 W. CONCLUSIONS Multiple PV foci are involved in initiation of AF, and elimination of PV muscle conduction is associated with clinical success.

Spectral Analysis Identifies Sites of High-Frequency Activity Maintaining Atrial Fibrillation in Humans

Background—The identification of sites of dominant activation frequency during atrial fibrillation (AF) in humans and the effect of ablation at these sites have not been reported. Methods and Results—Thirty-two patients undergoing AF ablation (19 paroxysmal, 13 permanent) during ongoing arrhythmia were studied. Electroanatomic mapping was performed, acquiring 126±13 points per patient throughout both atria and coronary sinus. At each point, 5-second electrograms were obtained to determine the highest-amplitude frequency on spectral analysis and to construct 3D dominant frequency (DF) maps. The temporal stability of the recording interval was confirmed in a subset. Ablation was performed with the operator blinded to the DF maps. The effect of ablation at sites with or without high-frequency DF sites (maximal frequencies surrounded by a decreasing frequency gradient ≥20%) was evaluated by determining the change in AF cycle length (AFCL) and the termination and inducibility of AF. The spatial distribution of the DF sites was different in patients with paroxysmal and permanent AF; paroxysmal AF patients were more likely to harbor the DF site within the pulmonary vein, whereas in permanent AF, atrial DF sites were more prevalent. Ablation at a DF site resulted in significant prolongation of the AFCL (180±30 to 198±40 ms; P<0.0001; &kgr;= 0.77), whereas in the absence of a DF site, there was no change in AFCL (169±22 to 170±22 ms; P=0.4). AF terminated during ablation in 17 of 19 patients with paroxysmal and 0 of 13 with permanent AF (P<0.0001). When 2 patients with nonsustained AF during mapping were excluded, 13 of 15 (87%) had AF termination at DF sites (54% at the initially ablated DF site): 11 pulmonary veins and 2 atrial. In addition, AF could no longer be induced in 69% with termination of AF at a DF site. There were no significant differences in the number or percentage of DF sites detected (5.4±1.6 versus 4.9±2.1; P=0.3) and ablated (1.9±1.0 versus 2.4±1.0; P=0.3) in those with and without AF termination. The duration of radiofrequency ablation to achieve termination was significantly shorter than that delivered in those with persisting AF (34.8±24.0 versus 73.5±22.9 minutes; P=0.0002). All patients with persisting AF had additional DF sites outside the ablated zones. Conclusions—Spectral analysis and frequency mapping identify localized sites of high-frequency activity during AF in humans with different distributions in paroxysmal and permanent AF. Ablation at these sites results in prolongation of the AFCL and termination of paroxysmal AF, indicating their role in the maintenance of AF.

Technique and Results of Linear Ablation at the Mitral Isthmus

Background—This prospective clinical study evaluates the feasibility and efficacy of combined linear mitral isthmus ablation and pulmonary vein (PV) isolation in patients with paroxysmal atrial fibrillation (AF). Methods and Results—One hundred consecutive patients (13 women; age 55±10 years) with drug-refractory, symptomatic paroxysmal AF underwent PV isolation and linear ablation of the cavotricuspid isthmus and the mitral isthmus (lateral mitral annulus to the left inferior PV). They were compared with 100 consecutive patients (14 women; age, 52±10 years) undergoing PV isolation and cavotricuspid ablation without mitral isthmus ablation. Bidirectional mitral isthmus block was confirmed by demonstrating (1) a parallel corridor of double potentials during coronary sinus (CS) pacing, (2) an activation detour by pacing either side of the line, and (3) differential pacing techniques. Isolation of all PVs and cavotricuspid isthmus ablation were performed successfully in all. Mitral isthmus block was achieved in 92 patients after 20±10 minutes of endocardial radiofrequency application and an additional 5±4 minutes of epicardial radiofrequency application from within the CS in 68, resulting in a conduction delay of 151±26 ms during CS pacing. Thirty-two patients with mitral isthmus ablation compared with 49 without had recurrent atrial arrhythmia (P=0.02) requiring further ablation. At 1 year after the last procedure, 87 patients with mitral isthmus ablation and 69 without (P=0.002) were arrhythmia free without antiarrhythmic drugs, mitral isthmus ablation being the only factor associated with long-term success (RR for AF recurrence, 0.2; CI, 0.1 to 0.4; P<0.001). Conclusions—Catheter ablation of the mitral isthmus results consistently in demonstrable conduction block and is associated with a high cure rate for paroxysmal AF.

Mapping and Ablation of Idiopathic Ventricular Fibrillation

Background— Ventricular fibrillation is the main mechanism of sudden cardiac death. The feasibility of eliminating recurrent episodes by catheter ablation has not been reported. Methods and Results— Twenty-seven patients without known heart disease (13 men, 14 women, 41±14 years of age) were studied after being resuscitated from recurrent (10±12) episodes of primary idiopathic ventricular fibrillation; 23 had received a defibrillator. The first initiating beat of ventricular fibrillation had an identical electrocardiographic morphology and coupling interval (297±41 ms) to preceding isolated premature beats typically noted in the aftermath of resuscitation. These triggers were localized by mapping the earliest electrical activity and ablated by local radiofrequency delivery. Outcome was assessed by Holter and defibrillator memory interrogation. Premature beats were elicited from the Purkinje conducting system in 23 patients: from the left ventricular septum in 10, from the anterior right ventricle in 9, an...

Detrimental Ventricular Remodeling in Patients With Congenital Complete Heart Block and Chronic Right Ventricular Apical Pacing

Background—Although dual-chamber pacing improves cardiac function in patients with complete congenital atrioventricular block (CCAVB) by restoring physiological heart rate and atrioventricular synchronization, the long-term detrimental effect of asynchronous electromechanical activation induced by apical right ventricular pacing (RVP) has not been well clarified. Methods and Results—Twenty-three CCAVB adults (24±3 years) with a DDD transvenous pacemaker underwent conventional echocardiography before implantation and, after at least 5 years of RVP, an exercise test and echocardiography coupled with tissue Doppler imaging and tissue tracking. They were compared with 30 matched healthy control subjects. After 10±3 years of RVP, CCAVB adults had significantly higher values versus controls in terms of intra–left ventricular (LV) asynchrony (respectively, 59±18 versus 19±9 ms, P<0.001), extent of LV myocardium displaying delayed longitudinal contraction (39±15% versus 10±7%, P<0.01), and septal-to-posterior wall-motion delay (84±26 versus 18±9 ms, P<0.01). The ratio of late-activated posterior to early-activated septal wall thickness was higher after long-term RVP than before (1.3±0.2 vs 1±0.1, P=0.05) and was higher than in controls (1±0.1, P<0.05). The percentage of patients with increased LV end-diastolic diameter was higher after long-term RVP than before implantation and was higher than in controls (57% versus 13%, P<0.05, and 57% versus 0%, P<0.01, respectively). CCAVB patients with long-term RVP had a lower cardiac output than controls (3.8±0.6 versus 4.9±0.8 L/min, P<0.05) and lower exercise performance (123±24 versus 185±39 W, P<0.001). Conclusions—Prolonged ventricular dyssynchrony induced by long-term endovenous RVP is associated with deleterious LV remodeling, LV dilatation, LV asymmetrical hypertrophy, and low exercise capacity. These new data highlight the importance of the ventricular activation sequence in all patients with chronic ventricular pacing.

Mapping and ablation of ventricular fibrillation associated with long-QT and Brugada syndromes.

Background—The long-QT and Brugada syndromes are important substrates of malignant ventricular arrhythmia. The feasibility of mapping and ablation of ventricular arrhythmias in these conditions has not been reported. Methods and Results—Seven patients (4 men; age, 38±7 years; 4 with long-QT and 3 with Brugada syndrome) with episodes of ventricular fibrillation or polymorphic ventricular tachycardia and frequent isolated or repetitive premature beats were studied. These premature beats were observed to trigger ventricular arrhythmias and were localized by mapping the earliest endocardial activity. In 4 patients, premature beats originated from the peripheral right (1 Brugada) or left (3 long-QT) Purkinje conducting system and were associated with variable Purkinje-to-muscle conduction times (30 to 110 ms). In the remaining 3 patients, premature beats originated from the right ventricular outflow tract, being 25 to 40 ms ahead of the QRS. The accuracy of mapping was confirmed by acute elimination of premature beats after 12±6 minutes of radiofrequency applications. During a follow-up of 17±17 months using ambulatory monitoring and defibrillator memory interrogation, no patients had recurrence of symptomatic ventricular arrhythmia but 1 had persistent premature beats. Conclusion—Triggers from the Purkinje arborization or the right ventricular outflow tract have a crucial role in initiating ventricular fibrillation associated with the long-QT and Brugada syndromes. These can be eliminated by focal radiofrequency ablation.

Changes in Atrial Fibrillation Cycle Length and Inducibility During Catheter Ablation and Their Relation to Outcome

Background—The modification of atrial fibrillation cycle length (AFCL) during catheter ablation in humans has not been evaluated. Methods and Results—Seventy patients undergoing ablation of prolonged episodes of AF were randomized to pulmonary vein (PV) isolation or additional ablation of the mitral isthmus. Mean AFCL was determined at a distance from the ablated area (coronary sinus) at the following intervals: before ablation, after 2- and 4-PV isolations, and after linear ablation. Inducibility of sustained AF (≥10 minutes) was determined before and after ablation. Spontaneous sustained AF (715±845 minutes) was present in 30 patients and induced in 26 (AFCL, 186±19 ms). PV isolation terminated AF in 75%, with the number of PVs requiring isolation before termination increasing with AF duration (P =0.018). PV isolation resulted in progressive or abrupt AFCL prolongation to various extents, depending on the PV: to 214±24 ms (P <0.0001) when AF terminated and to 194±19 ms (P <0.002) when AF persisted. The increase in AFCL (30±17 versus 14±11 ms; P =0.005) and the decrease in fragmentation (30.0±26.8% to 10.3±14.5%; P <0.0001) were significantly greater in patients with AF termination. Linear ablation prolonged AFCL, with a greater prolongation in patients with AF termination (44±13 versus 22±23 ms; P =0.08). Sustained AF was noninducible in 57% after PV isolation and in 77% after linear ablation. At 7±3 months, 74% with PV isolation and 83% with linear ablation were arrhythmia free without antiarrhythmics, which was significantly associated with noninducibility (P =0.03) with a recurrence rate of 38% and 13% in patients with and without inducibility, respectively. Conclusions—AF ablation results in a decline in AF frequency, with a magnitude correlating with termination of AF and prevention of inducibility that is predictive of subsequent clinical outcome.