2-year outcomes of phased radiofrequency ablation for atrial fibrillation with the second-generation PVAC Gold ablation catheter.

PURPOSE: The second-generation multi-electrode catheter, PVAC Gold, was designed to improve the safe delivery of phased radiofrequency energy using a "single shot" approach for pulmonary vein isolation (PVI), while retaining efficacy. This large registry presents long-term performance in a daily practice setting. METHODS: A total of 1011 patients undergoing first time ablation for atrial fibrillation (AF) using PVAC Gold were included, 639 patients with PVI for paroxysmal AF (PAF PVI) and 372 patients with persistent or long-standing persistent AF, divided into 175 patients receiving PVI only (PersAF PVI) and 197 patients receiving PVI with additional substrate ablation (PersAF PVI +). RESULTS: At 24-month follow-up, single procedure freedom from atrial tachyarrhythmia (ATA) was 58% (368/639) in the PAF PVI group, 44% (77/175) in the PersAF PVI group, and 29% (57/197) in the PersAF PVI + group. Allowing one repeat procedure in 33% of patients, 76%, 65%, and 54% were free from ATA at 24 months, respectively. Pulmonary vein reconnection was observed in 98% of patients with recurrent arrhythmia after PVI. CONCLUSIONS: Although phased RF ablation with PVAC Gold is quick and safe, the efficacy outcomes are modest compared to current mainstream ablation strategies.

Initial experience with AcQMap catheter for treatment of persistent atrial fibrillation and atypical atrial flutter.

INTRODUCTION: The AcQMap High Resolution Imaging and Mapping System was recently introduced. This system provides 3D maps of electrical activation across an ultrasound-acquired atrial surface. METHODS: We evaluated the feasibility and the acute and short-term efficacy and safety of this novel system for ablation of persistent atrial fibrillation (AF) and atypical atrial flutter. RESULTS: A total of 21 consecutive patients (age (mean ± standard deviation) 62 ± 8 years, 23% female) underwent catheter ablation with the use of the AcQMap System. Fourteen patients (67%) were treated for persistent AF and 7 patients (33%) for atypical atrial flutter. Eighteen patients (86%) had undergone at least one prior ablation procedure. Acute success, defined as sinus rhythm without the ability to provoke the clinical arrhythmia, was achieved in 17 patients (81%). At 12 months, 4 patients treated for persistent AF (29%) and 4 patients treated for atypical flutter (57%) remained in sinus rhythm. Complications included hemiparesis, for which intra-arterial thrombolysis was given with subsequent good clinical outcome (n = 1), and complete atrioventricular block, for which a permanent pacemaker was implanted (n = 2). No major complications attributable to the mapping system occurred. CONCLUSION: The AcQMap System is able to provide fast, high-resolution activation maps of persistent AF and atypical atrial flutter. Despite a high acute success rate, the recurrence rate of persistent AF was relatively high. This may be due to the selection of the patients with therapy-resistant arrhythmias and limited experience in the optimal use of this mapping system that is still under development.

High-density versus low-density mapping in ablation of atypical atrial flutter.

PURPOSE: Ablation of atypical atrial flutter (AAFL) can be challenging. High-density (HD) mapping of ablation targets may potentially increase procedural success and freedom from recurrent AAFL. The objective of the present study was to explore whether employing HD mapping leads to a more favorable outcome in ablation of AAFL. METHODS: We compared baseline and procedural characteristics, procedural success, safety and outcome of mapping and ablation of atypical flutter in three groups. (1) HD Grid catheter + the high-density electroanatomical mapping (EAM) system EnSite Precision; (2) standard 10-pole circular mapping catheter (CMC) + EnSite Precision; (3) CMC + the low-density EnSite Velocity EAM. Voltage and propagation maps were constructed. RESULTS: Mapping of 142 AAFL in 82 patients was performed. Acute ablation success was 78%, 68%, and 51% in groups 1, 2, and 3 (p = 0.037 between group 1 and 3, non-significant between groups otherwise). Moreover, 8%, 27%, and 36% of flutters were unmappable in groups 1, 2, and 3, respectively (p < 0.05 between group 1 and both groups 2 and 3). AAFL recurrence at 1-year FU was 26%, 36%, and 62% in groups 1, 2, and 3 (p = 0.007 between groups 1 and 3, p = 0.05 between groups 2 and 3). AAFL-free survival was significantly higher in patients mapped with Precision than with Velocity (p = 0.011). No strokes or mortality occurred within 30 days. CONCLUSIONS: Acute procedural success of ablation of atypical atrial flutter is higher and the number of unmappable flutters is lower using the HD Grid mapping catheter in combination with the high-density EnSite Precision system, as compared to a decapolar circular mapping catheter and the low-density EnSite Velocity EAM system. This may lead to increased freedom from recurrent AAFL at 1 year. HD mapping is safe.

Acute success and safety of the second-generation PVAC GOLD phased RF ablation catheter for atrial fibrillation.

PURPOSE: The second-generation multi-electrode catheter, pulmonary vein ablation catheter (PVAC) GOLD, was designed to improve the delivery of phased radiofrequency energy and reduce procedure times using a 'single-shot' approach for pulmonary vein isolation (PVI), while retaining efficacy and safety. This large registry presents acute success rates and safety outcomes in a daily practice setting. METHODS: A total of 1017 patients undergoing first-time ablation for atrial fibrillation (AF) using PVAC GOLD were included, 644 patients with paroxysmal AF and 373 patients with non-paroxysmal AF, divided into 175 patients receiving PVI only and 198 patients receiving PVI with additional substrate modification. RESULTS: High and comparable percentages of successful PVI could be achieved in all groups (98%, 95% and 99%; p = 0.108). The median total procedure time for all groups was 90 min [70-100]. As expected, the total procedure, ablation and fluoroscopy time were significantly longer in the PVI + substrate modification group compared with the PVI-only cases (all p < 0.001), but not between the PVI-only groups (p = 0.306, p = 0.088, p = 0.233, respectively). A total of 44 complications were observed in 43 patients (4.2%). Major complications were seen in 19 patients (1.87%) and non-major procedure-related complications were seen in 25 patients (2.46%). Complications leaving permanent sequelae were rare and occurred in only four patients (0.39%). Complications did not differ between groups (p = 0.199, p = 0.438, p = 0.240 and p = 0.465 respectively). CONCLUSION: PVAC GOLD performs successful PVI, while reducing procedure times and retaining safety for paroxysmal, persistent and long-standing persistent AF. Safety was unaffected by additional substrate modification.

Management and outcomes of real-world use of non-vitamin-K oral anticoagulants (NOACs) in patients with atrial fibrillation: experience of a dedicated NOAC clinic.

BACKGROUND: Current guidelines recommend non-vitamin­K oral anticoagulants (NOACs) as the first-choice therapy for stroke prevention in patients with atrial fibrillation (AF). The use of drugs in a clinical trial setting differs from that in real-world populations. Real-world data are important to accrue more heterogeneous patient populations with respect to co-morbidities and co-medication use. The aim of this study was to evaluate the use of NOACs in daily practice in a large tertiary hospital in the Netherlands. METHODS: A single-centre prospective study was conducted among all patients with AF using a NOAC in the St. Antonius Hospital between 2013 and June 2017. The outcomes were the rates of any bleeding, stroke/transient ischaemic attack, mortality, discontinuation rate and adverse drug reactions. RESULTS: In total, 799 patients were enrolled with a mean follow-up of 1.7 years. Mean age was 69.8 (SD ± 11) and 61.2% were male. Mean CHA2DS2-VASc score was 2.8 (SD ± 1.6) and mean HAS-BLED score was 1.4 (SD ± 0.9). Bleeding occurred in 6.0, major bleeding in 1.8, stroke in 1.2 patients per 100 patient-years, and 87 patients (10.9%) died during the follow-up period. Adverse drug reactions were reported by 59 patients (7.4%). Finally, 249 patients (31.2%) reported a temporary interruption and 132 (16.5%) permanent discontinuation of NOAC treatment, of whom 33 (25%) patients switched to a vitamin­K antagonist. CONCLUSIONS: We observed low rates of bleeding and adverse drug reactions. However, rates of mortality and discontinuation were relatively high. These results could possibly be explained by the real-world nature of the data including higher-risk patients.

Conduction recovery in patients with recurrent atrial fibrillation after pulmonary vein isolation using multi-electrode duty cycled radiofrequency ablation.

INTRODUCTION: The pulmonary vein ablation catheter (PVAC) is designed for pulmonary vein isolation (PVI). Electrical reconnection of pulmonary veins is believed to result in AF recurrence. The purpose of this study was to establish the location and extent of PV reconnection after PVI with the PVAC catheter. METHODS AND RESULTS: Eighty-two patients (79 % male, age 60 ± 9 years) that underwent a redo procedure for recurrent AF after PVAC ablation were assessed for prevalence and location of reconnection. The number of reconnected PV's was 0, 1, 2, 3, or 4 in 2 (2.4 %), 14 (17 %), 23 (28 %), 28 (34 %), and 15 (18 %) patients, respectively. Reconnection of left superior, left inferior, left common, right superior, and right inferior PV's was found in 66, 63, 83, 57, and 67 %, respectively (p = 0.48). In the left PV's, reconnection was located significantly more anterior than posterior; LSPV anterior 32/70 vs posterior 13/70 (p < 0.01), LIPV anterior 26/70 vs posterior 9/70 (p < 0.01). In the right PV's reconnection was distributed equally in all quadrants. Different modes of RF delivery during PVAC ablation (bipolar/unipolar 2:1 [n = 35] vs. 4:1 [n = 47]) yielded comparable rates of PV reconnection. During follow-up (median 296 days) no AF/AT was documented in 57 patients (70 %). CONCLUSION: Almost all patients (98 %) with AF after PVAC ablation show reconnection of at least one PV. All PV's are equally likely to show reconnection. In the left PV's, reconnection was found more often anteriorly than posteriorly. During pulmonary vein isolation with the PVAC catheter, prevalent sites of reconnection deserve close attention to increase success.

Internal atrial shock delivery by standard diagnostic electrophysiology catheters in goats: effects on atrial electrogram amplitude and tissue architecture.

AIMS: In this study, we evaluated the effects of atrial shock delivered via diagnostic electrophysiology catheters. METHODS AND RESULTS: In 11 anaesthetized goats, decapolar catheters were positioned in the right atrial appendage (RAA) and coronary sinus (CS). Three different catheters and two cardioversion protocols were evaluated. In four goats, 50 J shocks were delivered using catheters with 1 mm electrodes (surface area 70 mm(2)). In 6 goats, catheters with 2 mm electrodes (area 140 mm(2)) were used. In three of the six goats, 50 J shocks were given while in the other 3, 10 J shocks were delivered. In 1 goat 50 J shocks were delivered via 5 mm electrode catheters (area 310 mm(2)). No persisting adverse effects occurred. However, the electrogram amplitude at the RAA and CS decreased by >50-98% (P > 0.01). The amount of amplitude decrease was most pronounced at the CS site and for 50 J shocks. Goats were sacrificed after 9 +/- 1 days. Macroscopy revealed endocardial lesions at the electrode locations. Microscopy showed endocardial thrombosis, and necrosis with formation of granulation tissue. Changes were most marked with diagnostic catheters and 50 J shocks. CONCLUSIONS: Atrial shock delivery via diagnostic catheters causes local ablation lesions. The amount of amplitude decrease, macroscopic and microscopic damages were related to the energy applied and electrode surface area.

Development of the right ventricular inflow tract and moderator band: a possible morphological and functional explanation for Mahaim tachycardia.

Atriofascicular accessory bundles with AV-node like conduction properties can sustain atrioventricular (AV) re-entrant tachycardia (Mahaim tachycardia). During early embryogenesis, the AV canal is situated above the primitive left ventricle (LV), and a right AV connection has not been achieved yet. We studied the formation of the right ventricular (RV) inflow tract in relation to the developing cardiac conduction system and hypothesized a morphological explanation for functional atriofascicular bypass tracts. Analysis of lacZ-expression during sequential stages of cardiogenesis was performed in CCS-lacZ transgenic mice (E9.5 to 15.5). Embryos were stained for beta-galactosidase activity and the myocardial marker HHF35. At early stages CCS-lacZ expression was observed in a ring surrounding the AV canal, which connected at the inner curvature to the primary fold. The first sign of formation of the (CCS-lacZ negative) RV inlet component was a groove in the CCS-lacZ positive tissue of the primary fold. Outgrowth of the RV inlet tract resulted in division of the primary fold in a septal part, the trabecula septomarginalis and a lateral part, the moderator band, which extended laterally up to the right AV ring. Electrophysiological measurements in embryonic hearts (E15.5) in which the right atrium (RA) and RV were isolated from the left atrium (LA) and LV supported the functionality of this AV-connection via the moderator band, by demonstrating sequential atrial and ventricular activation in both RA/RV and LA/LV preparations. In conclusion, our observations may provide a possible morphological and functional explanation for atriofascicular accessory pathways via the moderator band, underlying Mahaim tachycardia.

Atrial fibrillation in the goat induces changes in monophasic action potential and mRNA expression of ion channels involved in repolarization.

INTRODUCTION: Sustained atrial fibrillation (AF) is characterized by a marked shortening of the atrial effective refractory period (AERP) and a decrease or reversal of its physiologic adaptation to heart rate. The aim of the present study was to investigate whether the AF-induced changes in AERP in the goat are associated with changes in the atrial monophasic action potential (MAP) and whether an abnormal expression of specific ion channels underlies such changes. METHODS AND RESULTS: Following thoracotomy, MAPs were recorded from the free wall of the right atrium both before induction of AF (control) and after cardioversion of sustained AF (>2 months) in chronically instrumented goats. In control goats, MAP duration at 80% repolarization (MAPD80) shortened (P < 0.01) from 132+/-4 msec during slow pacing (400-msec interval) to 86+/-10 msec during fast pacing (180 msec). After cardioversion of sustained AF, the MAPD80 during slow pacing was as short as 67+/-5 msec (electrical remodeling). Increasing the pacing rate resulted in prolongation (P = 0.02) of the MAPD80 to 91+/-6 msec. Also, MAPD20 (20% repolarization) shortened (P = 0.05) from 32+/-4 msec (400 msec) to 14+/-7 msec (180 msec) in the control goats, whereas it prolonged (P = 0.03) from 20+/-3 msec (400 msec) to 33+/-5 msec (180 msec) in sustained AF. mRNA expression of the L-type Ca2+ channel alpha1c gene and Kv1.5 potassium channel gene, which underlie ICa and IKur, respectively, was reduced in sustained AF compared with sinus rhythm by 32% (P = 0.01) and 45% (P < 0.01), respectively. No significant changes were found in the mRNA levels of the rapid Na+ channel, the Na+/Ca2+ exchanger, or the Kv4.2/4.3 channels responsible for Ito. CONCLUSION: AF-induced electrical remodeling in the goat comprises shortening of MAPD and reversal of its physiologic rate adaptation. Changes in the time course of repolarization of the action potential are associated with changes in mRNA expression of the alpha subunit genes of the L-type Ca2+ channel and the Kv1.5 potassium channel.

Widening of the excitable gap during pharmacological cardioversion of atrial fibrillation in the goat: effects of cibenzoline, hydroquinidine, flecainide, and d-sotalol.

BACKGROUND: Previous studies suggest that the antifibrillatory action of class I and III drugs is due to prolongation of the atrial wavelength. The aim of the present study was to directly evaluate the electrophysiological action of antifibrillatory drugs in a goat model of chronic atrial fibrillation (AF). METHODS AND RESULTS: Six goats were instrumented with multiple atrial electrodes, and sustained AF was induced by electrical remodeling. During sustained AF, the effects of intravenous infusion of cibenzoline, hydroquinidine, flecainide, and d-sotalol on AF cycle length (AFCL), refractory period (RP(AF)), conduction velocity (CV(AF)), pathlength (PL(AF)), wavelength (WL(AF)), temporal (AFCL-RP(AF)), and spatial (PL(AF)-WL(AF)) excitable gap were studied. The RP(AF) was measured by determining the earliest moment at which single stimuli could capture the fibrillating atria. CV(AF) was measured during regional entrainment of AF. Contrary to our expectation, cardioversion of AF could not be attributed to prolongation of WL(AF). Hydroquinidine and d-sotalol did not affect WL(AF) significantly, whereas cibenzoline and flecainide even shortened WL(AF) by 18% and 36%, respectively. PL(AF) was increased by hydroquinidine and d-sotalol by 30%, whereas cibenzoline and flecainide did not prolong PL(AF). The only parameter that correlated consistently with cardioversion of AF was a widening of the temporal excitable gap (cibenzoline 176%, hydroquinidine 105%, flecainide 86%, d-sotalol 88%). CONCLUSIONS: Pharmacological cardioversion of AF cannot be explained by prolongation of WL(AF). An alternative explanation for the antifibrillatory effect of class I and III drugs may be a widening of the temporal excitable gap.

Pharmacologic cardioversion of chronic atrial fibrillation in the goat by class IA, IC, and III drugs: a comparison between hydroquinidine, cibenzoline, flecainide, and d-sotalol.

INTRODUCTION: Recently, we reported that repetitive induction of atrial fibrillation (AF) in the goat causes electrical remodeling of the atria leading to the development of sustained AF. The aim of the present study was to compare Class IA, IC, and III drugs in their ability to cardiovert chronic AF in remodeled atria. METHODS AND RESULTS: In 16 goats with sustained AF, hydroquinidine (HQ), cibenzoline (Ci), flecainide (FI), and d-sotalol (dS) were infused. HQ, Ci, Fl, and dS restored sinus rhythm (SR) in 83%, 91%, 67%, and 92% of the cases, while adverse drug effects occurred in 17%, 36%, 56%, and 8%. Prior to restoration of SR, AF cycle length prolonged by 68%, 103%, 53%, and 20%, respectively. The QRS width increased by 14%, 64%, and 58% (HQ, Ci, and Fl), and remained unchanged by administration of dS. RR intervals were slightly prolonged by HQ, Ci, and Fl, and markedly prolonged by dS (48%). The QT interval was moderately prolonged by HQ, Ci, and Fl, and considerably by dS (34%). QTc was only slightly prolonged by each of the drugs. Directly after cardioversion of AF, the atrial refractory period was 87+/-29 (HQ), 119+/-32 (Ci), 66+/-10 (Fl), and 73+/-18 msec (dS) (control: 146+/-18 msec). Atrial conduction velocity was 85+/-6, 71+/-11, 86+/-12, and 110+/-11 cm/sec compared with a control value of 116+/-10 cm/sec. Because directly after cardioversion the atrial wavelength was still very short (5.7 to 8.4 cm), the vulnerability for AF was still very high, and a single premature beat reinduced AF in 71% (Ci) to 100% (HQ, Fl, and dS) of the cases. CONCLUSION: In a goat model of sustained AF, Class IA, IC, and III drugs restored sinus rhythm in 67% to 92% of the cases. However, after cardioversion, the atrial wavelength was still abnormally short, and AF was readily inducible in 71% to 100% of the cases.

Mechanisms of pharmacologic cardioversion of atrial fibrillation by Class I drugs.

INTRODUCTION: We recently developed a goat model of sustained atrial fibrillation (AF) in which repetitive induction of AF by burst pacing shortened the atrial effective refractory period (AERP) (electrophysiologic remodeling) and progressively prolonged the paroxysms of AF to become sustained (24 hours) within 1 to 3 weeks (atrial fibrillation begets atrial fibrillation). The aim of the present study was to study the effect of Class I drugs in this animal model of chronic AF. METHODS AND RESULTS: The effects of hydroquinidine (HQ) on seven chronically fibrillating goats and of flecainide (Fl) on nine goats were studied. Both drugs were infused intravenously until sustained AF was cardioverted or adverse drug effects occurred. HQ and Fl restored sinus rhythm in 86% and 67% of the cases. Adverse drug effects occurred in 14% and 56%, respectively. The average atrial cycle length of AF (AFCL) was prolonged to a different degree. Just before restoration of sinus rhythm, the two drugs had increased AFCL by 72% and 50%. The duration of the QRS complex was prolonged 17% by HQ and 50% by Fl. The RR interval was not affected by HQ and was prolonged slightly by Fl. Directly after restoration of sinus rhythm, the AERP during pacing with an interval of 400 msec was 92 +/- 29 (HQ) and 66 +/- 10 msec (Fl) (control value: 149 +/- 10 msec). Intra-atrial conduction velocity was 83 +/- 7 and 86 +/- 11 cm/sec (control value: 116 +/- 10 cm/sec). Although both drugs were effective in terminating AF, after cardioversion the atrial vulnerability was still very high and a single premature stimulus reinduced AF in 100% of the animals. As a result of the short AERP by the AF-induced remodeling and the depressed intra-atrial conduction by the Class I drugs, directly after cardioversion the atrial wavelength was abnormally short (between 5.7 and 7.5 cm). This explains the still high atrial vulnerability to AF directly after cardioversion by Class I drugs. Surprisingly, the prolongation of AFCL by either Class I drug was not due to lengthening of the functional refractory period but rather to a widening of the excitable gap during AF. CONCLUSION: In a goat model of chronic AF, infusion of Class IA and Class IC drugs restored sinus rhythm in 67% to 86% of the cases. However, due to the short AERP and the depressed intra-atrial conduction directly after cardioversion, the atrial vulnerability was still very high and a premature beat easily reinduced AF.

Altered pattern of connexin40 distribution in persistent atrial fibrillation in the goat.

INTRODUCTION: Since altered expression of gap junction proteins (connexins) in diseased myocardial tissue may lead to abnormal electrical coupling between cardiomyocytes and hence contribute to arrhythmogenesis, the expression of connexin(Cx)40 and Cx43 was studied in atrial appendage from goats in sinus rhythm (SR) and persistent atrial fibrillation (AF). METHODS AND RESULTS: Biopsies were taken from the left and right atrial appendages from goats in SR or after pacing-induced persistent AF. Analyses of Cx40 and Cx43 mRNA and protein levels, using quantitative (competitive) polymerase chain reaction and western blotting, respectively, revealed no significant changes in the overall expression of Cx40 and Cx43 as a result of persistent AF. At the cellular level, immunohistochemistry and confocal laser scanning microscopy showed a homogeneous distribution of either connexin in atrial sections taken during SR. After induction of AF, the distribution of Cx43 gap junctions was unchanged whereas the Cx40 pattern showed marked inhomogeneities with small areas (0.15 to 0.6 mm in diameter, 25% of section surface area) of low-density Cx40 located between larger areas of normal (unchanged) Cx40 density. Activation mapping (244 electrodes, spatial resolution 2.25 mm) of the right atrial wall did not reveal changes in atrial conduction velocity. CONCLUSION: Pacing-induced persistent AF in the goat gave rise to changes in the spatial organization of Cx40 gap junctions. Although the overall conduction velocity appeared not to have changed, microheterogeneities in conduction due to the local redistribution of Cx40 gap junctions might have contributed to the initiation and maintenance of AF.

Electrical remodeling due to atrial fibrillation in chronically instrumented conscious goats: roles of neurohumoral changes, ischemia, atrial stretch, and high rate of electrical activation.

BACKGROUND: Recently, we developed a goat model of chronic atrial fibrillation (AF). Due to AF, the atrial effective refractory period (AERP) shortened and its physiological rate adaptation inversed, whereas the rate and stability of AF increased. The goal of the present study was to evaluate the role of (1) the autonomic nervous system, (2) ischemia, (3) stretch, (4) atrial natriuretic factor (ANF), and (5) rapid atrial pacing in this process of electrical remodeling. METHODS AND RESULTS: Twenty-five goats were chronically instrumented with multiple epicardial atrial electrodes. Infusion of atropine (1.0 mg/kg; n=6) or propranolol (0.6 mg/kg; n=6) did not abolish the AF-induced shortening of AERP or interval (AFI). Blockade of K+(ATP) channels by glibenclamide (10 micromol/kg; n=6) slightly increased the AFI from 95+/-4 to 101+/-5 ms, but AFI remained considerably shorter than during acute AF (145 ms). Glibenclamide had no significant effect on AERP after electrical cardioversion of AF (69+/-14 versus 75+/-15 ms). Volume loading by 0.5 to 1.0 L of Hemaccel (n=12) did not shorten AERP. The median plasma level of ANF increased from 42 to 99 pg/mL after 1 to 4 weeks of AF (n=6), but ANF infusion (0.1 to 3.1 microg/min, n=4) did not shorten AERP. Rapid atrial pacing (24 to 48 hours; n=10) progressively shortened AERP from 134+/-10 to 105+/-6 ms and inversed its physiological rate adaptation. CONCLUSIONS: Electrical remodeling by AF is not mediated by changes in autonomic tone, ischemia, stretch, or ANF. The high rate of electrical activation itself provides the stimulus for the AF-induced changes in AERP.

Verapamil reduces tachycardia-induced electrical remodeling of the atria.

BACKGROUND: Prolonged periods of atrial fibrillation or rapid atrial pacing induce shortening of the atrial effective refractory period (AERP), which is thought to be related to the lower success rates of various antifibrillatory treatments when the arrhythmia has lasted for a longer period of time. METHODS AND RESULTS: To investigate whether an increase in intracellular calcium could be the stimulus for electrical remodeling, the effects of verapamil on shortening of the AERP in response to 24 hours of rapid atrial pacing (300 bpm) were studied in five chronically instrumented conscious goats during infusion of saline or verapamil. During rapid atrial pacing, the ventricular rate was kept constant by ventricular pacing (150 bpm). The AERP was measured by programmed electrical stimulation at basic cycle lengths of 430, 300, and 200 ms. Verapamil had no effects on the AERP before rapid atrial pacing. However, in the course of 24 hours of rapid atrial pacing, the AERP shortened significantly less (27% to 58%) in the presence of verapamil compared with control (at 430, 300, and 200 ms, P < .001, P < .01, and P < .01, respectively). Also, after cessation of pacing, complete recovery of the AERP during verapamil infusion occurred much sooner than in the control experiments. Despite a significant reduction in electrical remodeling, there was only a minimal reduction in inducibility of atrial fibrillation by verapamil (34% versus 39% in the control experiments, P = .03). CONCLUSIONS: Electrical remodeling of the atrium during rapid atrial pacing was significantly attenuated by verapamil. This suggests that electrical remodeling of the atrium is triggered by the high calcium influx during rapid atrial pacing rates.

Atrial fibrillation begets atrial fibrillation. A study in awake chronically instrumented goats.

BACKGROUND: In this study we tested the hypothesis that atrial fibrillation (AF) causes electrophysiological changes of the atrial myocardium which might explain the progressive nature of the arrhythmia. METHODS AND RESULTS: Twelve goats were chronically instrumented with multiple electrodes sutured to the epicardium of both atria. Two to 3 Weeks after implantation, the animals were connected to a fibrillation pacemaker which artificially maintained AF. Whereas during control episodes of AF were short lasting (6 +/- 3 seconds), artificial maintenance of AF resulted in a progressive increase in the duration of AF to become sustained (> 24 hours) after 7.1 +/- 4.8 days (10 of 11 goats). During the first 24 hours of AF the median fibrillation interval shortened from 145 +/- 18 to 108 +/- 8 ms and the inducibility of AF by a single premature stimulus increased from 24% to 76%. The atrial effective refractory period (AERP) shortened from 146 +/- 19 to 95 +/- 20 ms (-35%) (S1S1, 400 ms). At high pacing rates the shortening was less (-12%), pointing to a reversion of the normal adaptation of the AERP to heart rate. In 5 goats, after 2 to 4 weeks of AF, sinus rhythm was restored and all electrophysiological changes were found to be reversible within 1 week. CONCLUSIONS: Artificial maintenance of AF leads to a marked shortening of AERP, a reversion of its physiological rate adaptation, and an increase in rate, inducibility and stability of AF. All these changes were completely reversible within 1 week of sinus rhythm.

Experimental models of arrhythmias: toys or truth?

In this communication two new experimental models of atrial fibrillation are described. One model (artificial maintenance of atrial fibrillation in conscious goats) points to the electrophysiological changes caused by prolonged atrial fibrillation. It shows that within 24 h of atrial fibrillation the atrial refractory period becomes markedly shortened and the duration of atrial fibrillation markedly prolonged. In the other model, experimentally induced atrial fibrillation in the dog is regionally entrained by local rapid pacing. However, termination of atrial fibrillation by local overdrive pacing was never observed. The possible implication of these new experimental models for prevention and treatment of clinical atrial fibrillation are discussed.