Arif Elvan

Pacing-Induced Chronic Atrial Fibrillation Impairs Sinus Node Function in Dogs Electrophysiological Remodeling

BACKGROUND We assessed the effects of pacing-induced chronic atrial fibrillation (AF) on sinus node function, intra-atrial conduction, and atrial refractoriness. METHODS AND RESULTS In 15 mongrel dogs (20 to 30 kg), AV nodal block was produced by radiofrequency catheter ablation, and a ventricular-inhibited (VVI) pacemaker (Minix 8330, Medtronic) was implanted and programmed to pace at 80 pulses per minute. In 11 of these dogs, right atrial endocardial pacing leads were connected to a pulse generator (Itrel 7432, Medtronic) and set at a rate of 20 Hz to induce AF. Corrected sinus node recovery time, P-wave duration, 24-hour Holter ECG to assess AF duration, maximal heart rate in response to isoproterenol (10 micrograms/min), intrinsic heart rate after administration of atropine (0.04 mg/kg) and propranolol (0.1 mg/kg), and atrial effective refractory periods (ERPs) were obtained at baseline (EPS-1) and after 2 to 6 weeks (EPS-2) of VVI pacing alone (n = 4) or VVI pacing and rapid atrial pacing (n = 11). At EPS-2, corrected sinus node recovery time and P-wave duration were prolonged, maximal heart rate and intrinsic heart rate were decreased, atrial ERPs were shortened, and the duration of AF was increased significantly compared with EPS-1. These changes partially reversed toward baseline 1 week after conversion to sinus rhythm. Sinus node function and AF inducibility observed in the control dogs that underwent ventricular pacing alone (n = 4) did not change. CONCLUSIONS Pacing-induced chronic AF induces sinus node dysfunction, prolongs intra-atrial conduction time, shortens atrial refractoriness, and perpetuates AF, changes that reverse gradually after termination of AF.

Radiofrequency catheter ablation of the atria reduces inducibility and duration of atrial fibrillation in dogs

BACKGROUND The purpose of this study was to prevent induction of sustained atrial fibrillation (AF) by radiofrequency catheter ablation (RFCA) of the atria in an open-chest canine model. METHODS AND RESULTS In dogs randomized to acute studies, RFCA of the atria was performed after reproducible induction of sustained AF (lasting > 30 minutes) with burst stimulation or premature atrial pacing and perpetuation by low level cervical vagal stimulation or IV infusion of methacholine. Additionally, in four dogs, the long-term effectiveness of RFCA was assessed 7 to 21 days after ablation. Continuous discrete transmural lesions were produced with radiofrequency energy pulses (20 to 40 W for 60 seconds) delivered to five atrial epicardial sites and endovascularly to the coronary sinus wall. RFCA electrically isolated regions of the atria that became dissociated from the nonisolated parts. Atrial RFCA markedly attenuated vagally induced shortening of effective refractory period (ERP) at both isolated and nonisolated test sites located in the left and right atria (P < .001, n = 5). RFCA rendered noninducible sustained AF maintained by cervical vagal stimulation. The dose-response curve relating the dose of methacholine required to maintain AF was shifted down and to the right. AF was only inducible with high doses of methacholine. Atrial RFCA reduced the maximal sinus rate and prolonged the corrected sinus-node recovery time (P < .001, n = 6). However, RFCA did not affect atrial contractile function, AV-nodal ERP, or AV-nodal or His-Purkinje conduction times. In dogs in the chronic group, normal sinus rhythm and normal AV conduction were preserved and AF was only inducible with a high dose of methacholine. No atrial perforations resulted. CONCLUSIONS RFCA in open-chest dogs produces partial vagal denervation and reduces the inducibility of AF.

Radiofrequency Catheter Ablation of the Atria Eliminates Pacing-Induced Sustained Atrial Fibrillation and Reduces Connexin 43 in Dogs

BACKGROUND We assessed the effects of radiofrequency catheter ablation (RFCA) of the atrial epicardium on pacing-induced sustained atrial fibrillation (AF) and the expression and distribution of the intercellular gap junction protein connexin 43 (Cx43) in dogs. METHODS AND RESULTS In 12 mongrel dogs, after creation of complete AV block and implantation of a ventricular inhibited pacemaker, a high-rate pulse generator (20 to 30 Hz to induce AF) was implanted in the neck, connected to a right atrial endocardial pacing lead, and used to pace the atrium for 10 to 14 weeks. In group 1 (n=9 dogs), corrected sinus node recovery time (CSNRT), P-wave duration, 24-hour Holter ECG, maximal heart rate (MHR) in response to isoproterenol, and intrinsic heart rate (IHR) after atropine (0.04 mg/kg) and propranolol were measured before and after atrial pacing and RFCA. Group 2 dogs were used to assess the effect of chronic AF alone on Cx43 expression and distribution. All group 1 dogs developed sustained (>24 hours) AF. Right-sided RFCA of the atria eliminated the sustained AF in 5 dogs, but both right and left atrial RFCA was required to abolish sustained AF in the other 4 dogs. After RFCA restored sinus rhythm, CSNRT and P-wave duration were prolonged and MHR and IHR were decreased. Chronic rapid atrial pacing (group 2) increased the expression of Cx43, which was absent in ablated areas and markedly depressed in viable atrial myocytes near the ablation zones (group 1). CONCLUSIONS Rapid atrial pacing for long time periods induced sustained AF that can be eliminated by linear right and left atrial lesions created with RFCA, with preservation of sinus rhythm and atrial contractile function. Chronic AF increased the expression and distribution of gap junction protein Cx43, which became reduced in ablated and nearby nonablated areas.

Successful Radiofrequency Ablation in Patients With Previous Atrial Fibrillation Results in a Significant Decrease in Left Atrial Size

Background— The objective of the present study was to evaluate the relation between freedom from atrial fibrillation (AF) and left atrial (LA) size in patients who underwent circumferential pulmonary vein (PV) isolation and LA ablation. Methods and Results— One hundred five consecutive patients with symptomatic and drug-refractory paroxysmal or persistent AF were included in the present study. The mean age was 52±9.5 years (range, 27 to 75 years); 74 patients (70%) were male. Paroxysmal AF was present in 52 (49.5%) and persistent AF in 53 (50.5%) patients. Mean AF duration was 6.0±5.1 years in the paroxysmal AF group and 7.6±6.0 years in the persistent AF group. A 3D electroanatomic map of the LA including the PV ostia was constructed with a nonfluoroscopic navigation system (Carto, Biosense Webster). Left- and right-sided PVs were encircled by continuous radiofrequency ablation lines. We performed 128 ablation procedures in 105 patients, ie, 23 redo procedures. The mean long-term follow-up duration was 14.6±4.9 months (range, 6 to 24 months). Sinus rhythm was present in 45 patients (86.5%) in the paroxysmal AF group and in 41 patients (77.3%) in the persistent AF group at the latest follow-up. Six months after ablation, LA dimension in the persistent AF subjects who remained in sinus rhythm decreased from 44.0±5.8 to 40±4.5 mm (range, 31 to 51 mm). In contrast, in patients with recurrences of AF, LA dimension increased from 45±6.5 to 49±5.4 mm (range, 32 to 59 mm). In the successfully treated paroxysmal AF group, LA dimension decreased from 40.5±4.4 to 37.5±3.5 mm (P<0.01). Conclusions— In radiofrequency ablation of AF using an electroanatomic approach, there is a statistically significant relationship between medium-term procedural success and LA size: persistent sinus rhythm is associated with reduced and recurrent AF with increased LA dimensions.

Identification of the Substrate of Atrial Vulnerability in Patients With Idiopathic Atrial Fibrillation

BACKGROUND Experimental studies have shown that atrial fibrillation (AF) causes remodeling, which facilitates AF perpetuation. AF may also, however, occur in patients without remodeling and underlying structural cardiac disease. The substrate for enhanced vulnerability in these patients is unknown. METHODS AND RESULTS We studied 43 patients without structural heart disease: 18 patients with documented sporadic paroxysmal AF and 25 control patients without AF. In each patient, a decapolar catheter was positioned against the right atrial free wall, and a quadripolar catheter was positioned in the right atrial appendage. Unipolar electrograms were recorded. Atrial vulnerability was assessed according to an increasingly aggressive stimulation protocol. Mean local fibrillatory interval (FI) was used as an index of local refractoriness. Spatial dispersion of refractoriness was assessed through the calculation of the coefficient of dispersion (CD), which was defined as the SD of mean local FI expressed as a percentage of the mean FI. In the AF group, AF was induced with a single extrastimulus in 16 of 18 patients; the CD was 5.4+/-2.6, and the mean FI was 164+/-29 ms. In the control group, AF could be induced only with more aggressive pacing in 23 of the 25 patients; the CD was 1.4+/-0.7 (P<0.0001), and the mean FI was 175+/-26 ms (NS). CONCLUSIONS Patients with idiopathic AF showed increased dispersion of refractoriness, which may be the substrate for the observed enhanced inducibility and spontaneous occurrence of AF.

Efficacy of multi-electrode duty-cycled radiofrequency ablation for pulmonary vein disconnection in patients with paroxysmal and persistent atrial fibrillation

AIM A novel multi-electrode pulmonary vein ablation catheter (PVAC) combining circular mapping and duty-cycled multi-electrode radiofrequency (RF) energy delivery has been developed to map and isolate the pulmonary veins (PVs). The aim of this study was to assess the efficacy of multi-electrode RF ablation using the PVAC device. METHODS AND RESULTS A total of 102 consecutive patients, age 57.9 +/- 9.6 years, with paroxysmal or persistent drug refractory atrial fibrillation (AF) were referred for ablation. All patients had documented AF episodes with an AF duration of 9.3 +/- 7.5 years (range 1.5-25). The mean total procedure time was 139.30 +/- 37.72 (median 135, range 115-172). The mean fluoroscopy time required for PVAC ablation was 17 +/- 12 min (median 16, range 12-33) and the total fluoroscopy time was 32.1 +/- 11.3 min (median 29, range 25-39). The mean multi-electrode RF ablation time required to achieve complete PV isolation was 31 +/- 6.7 min (range 16-51). In eight patients with persistent AF, additional ablations were performed to defragment septal and posterior part of the left atrium. In five patients additional RF ablations using conventional catheters were necessary. After multi-electrode duty-cycled RF ablation, 62 of 102 (60.8%) patients were in sustained sinus rhythm without anti-arrhythmic drugs. The mean follow-up duration was 12.2 +/- 3.9 months (range 6-15). CONCLUSION This novel multi-electrode ablation technique can be used for PV isolation and left atrium ablation with a relatively low medium-term success rate after the first ablation of approximately 61%. Larger studies with longer follow-up are required to evaluate the efficacy and whether multi-electrode RF ablation is associated with a different complication rate compared with standard PV isolation.

Prevalence and presentation of externalized conductors and electrical abnormalities in Riata defibrillator leads after fluoroscopic screening: report from the Netherlands Heart Rhythm Association Device Advisory Committee.

Background— The Riata family of implantable cardioverter-defibrillator (ICD) leads is prone to a specific insulation abrasion characterized by externalization of conductor cables. The objective of this study was to determine the prevalence of externalized conductors and electrical abnormalities in Riata ICD leads by fluoroscopic screening and standard ICD interrogation. Methods and Results— All ICD implantation centers were contacted by the Netherlands Heart Rhythm Association Device Advisory Committee to identify all patients with an active Riata ICD lead and to perform fluoroscopic screening of the lead. In addition, the electrical integrity of the lead was assessed. As of March 1, 2012, data for 1029 active Riata leads were available; 47% of these were 8-F Riata and 53% were 7-F Riata ST. Externalized conductors were observed in 147 leads (14.3%). Proportion of externalized conductors was higher in 8-F Riata compared with 7-F Riata ST (21.4% vs 8.0%; P<0.001). Median time from implantation to detection of externalized conductors was 65.3 months. The estimated rates of externalized conductors were 6.9% and 36.6% at 5 and 8 years after implantation, respectively. Of the 147 leads with externalized conductors, 10.9% had abnormal electrical parameters vs 3.5% in nonexternalized leads (P<0.001). Conclusions— The prevalence of externalized conductors in Riata leads is significantly high (14.3%) using fluoroscopic screening. The majority of externalized conductors are not detectable with standard ICD interrogation. Screening with fluoroscopy is reasonable.

Dominant frequency of atrial fibrillation correlates poorly with atrial fibrillation cycle length.

Background—Localized sites of high frequency during atrial fibrillation (AF) are used as target sites to eliminate AF. Spectral analysis is used experimentally to determine these sites. The purpose of this study was to compare dominant frequencies (DF) with AF cycle length (AFCL) of unipolar and bipolar recordings. Methods and Results—Left and right atrial endocardial electrograms were recorded during AF in 40 patients with lone AF, using two 20-polar catheters. Mean age was 53±9.9 years. Unipolar and bipolar electrograms were recorded simultaneously during 16 seconds at 2 right and 4 left atrial sites. AFCLs and DFs were determined. QRS subtraction was performed in unipolar signals. DFs were compared with mean, median, and mode of AFCLs; 4800 unipolar and 2400 bipolar electrograms were analyzed. Intraclass correlation was poor for all spectral analysis protocols. Best correlation was accomplished with DFs from unipolar electrograms compared with median AFCL (intraclass correlation coefficient, 0.67). A gradient in median AFCL of >25% was detected in 16 of 40 patients. In 13 of 16 patients (81%) with a frequency gradient of >25%, the site with highest frequency was located in the left atrium (posterior left atrium in 8 patients). The site with shortest median AFCL and highest DF corresponded in 25% if unipolar and in 31% if bipolar electrograms were analyzed. Conclusions—DFs from unipolar and bipolar electrograms recorded during AF correlated poorly with mean, median, and mode AFCL. If a frequency gradient >25% existed, the site with highest DF corresponded to the site of shortest median AFCL in only 25% of patients. Because spectral analysis is being used to identify ablation sites, these data may have important clinical implications.

Predictive factors of sustained sinus rhythm and recurrent atrial fibrillation after a radiofrequency modified Maze procedure

BACKGROUND Preoperative atrial fibrillation (AF) in patients scheduled for elective open-heart surgery is a well-known phenomenon. The cut and sew Maze procedure or variant Maze procedures abolish AF in 45-95% of patients during short- to intermediate-term follow-up. We determined preoperative and postoperative factors predictive of sustained sinus rhythm (SR) and recurrent AF in an elderly cohort of patients with structural heart disease who underwent cardiac surgery. PATIENTS AND METHODS From November 1995 to November 2003, 285 patients with structural heart disease and permanent AF were scheduled for elective cardiac surgery. All patients underwent a radiofrequency (RF) modified Maze procedure as an adjunct to the open-heart operation. Patients were followed in the outpatient clinic or follow-up data were obtained from attending doctors. Patients are being followed in an ongoing registry; however for the patients who are the subject of this paper follow-up ended November 2006. Preoperative factors predicting recurrent AF postoperatively were assessed, as were factors associated with sustained SR. RESULTS Two hundred and eighty-five patients (mean age 68.0+/-9.6 years) underwent a total of 655 open-heart procedures and concomitant RF Maze surgery. In-hospital mortality was 4.6% (13 patients). Mean and median duration of AF were 60.9+/-68.7 months and 26 months (range 6-396), respectively. Median follow-up was 36.5 months (range 27-114 months). Sustained SR, including atrial rhythm or an atrial-based paced rhythm was present in 59% of patients at 1 year, in 54.4% at 3 years, in 53.4% at 5 years and in 57.1% of patients at the latest follow-up. Stroke was reported in six patients (2.1%). Factors predictive of postoperative AF recurrence were duration of permanent AF, preoperative atrial fibrillation wave and preoperative left atrial (LA) size. Postoperative angiotensin converting enzyme (ACE) inhibitor therapy was associated with SR during follow-up. LA size decreased during follow-up in patients with sustained SR, whereas LA size increased in case of recurrent AF. CONCLUSIONS In this group of elderly patients with permanent AF in the setting of structural heart disease who underwent cardiac surgery and a RF Maze procedure as a concomitant procedure, the duration of AF, preoperative atrial fibrillation wave and preoperative LA size were predictive of recurrent AF, whereas left ventricular ejection fraction, left ventricular diameters and invasive hemodynamic parameters were not. Postoperative ACE inhibitor therapy was associated with sustained SR. Furthermore, sustained SR after RF Maze surgery was associated with decreased LA dimensions.

Intermediate to Long-Term Results of Radiofrequency Modified Maze Procedure as an Adjunct to Open-Heart Surgery

BACKGROUND Of patients scheduled for elective open heart surgery, a substantial number of patients have preoperative atrial fibrillation (AF). The cut-and-sew Maze procedure and variant Maze procedures abolish AF in 45% to 95% during short- to intermediate-term follow-up. Limited data are available about maintenance of sinus rhythm during intermediate- to long-term follow-up. The objective of the present study was to assess the association between postoperative rhythm and mortality and stroke. METHODS From November 1995 to November 2003, 258 patients with structural heart disease and permanent AF with a duration of longer than 12 months were scheduled for elective cardiac surgery and included in a registry. They underwent a radiofrequency modified Maze procedure as an adjunct to the open heart operation. Patients were followed in the outpatient clinic, and follow-up data were obtained from medical correspondence of attending physicians. For this paper, follow-up ended November 2006; however, patients are being followed in an ongoing registry. RESULTS Two hundred fifty-eight patients (mean age, 68.1 +/- 9.5 years) with permanent AF underwent cardiac surgical procedures and concomitant radiofrequency Maze surgery; 213 patients (82.5%) underwent more than one procedure. Mean duration of permanent AF was 66.6 +/- 69.8 months (range, 16 to 96). Preoperatively, 82.9% of patients were in New York Heart Association class III. In-hospital mortality was 3.9% (10 patients), and during a mean follow-up of 43.7 +/- 25.9 months (range, 27 to 114), 73 patients (28.3%) died. Left ventricular ejection fraction was normal in 44.6%, moderately decreased in 42.5%, and poor in 12.9% of patients. Sustained sinus rhythm, including atrial rhythm or an atrial-based paced rhythm was present in 69% of patients at 1 year, in 56% at 3 years, in 52% at 5 years, and in 57% of patients at the latest follow-up. Antiarrhythmic drugs were used by 64% of survivors who were free of atrial fibrillation. Oral anticoagulation therapy was taken by 99% of patients. Stroke was reported in 4 patients (1.6%). CONCLUSIONS The RF modified Maze procedure abolishes AF in the majority of patients with structural heart disease and longstanding permanent AF. Postoperative rhythm was not predictive of all-cause mortality, cardiac mortality, and stroke, neither in the whole group nor in the subgroups defined by preoperative left ventricular ejection fraction and New York Heart Association class. The stroke rate was very low in this group with longstanding AF.