Electrophysiologic approach to diagnosis and ablation of patients with permanent junctional reciprocating tachycardia associated with complex anatomy and/or physiology.

INTRODUCTION: Permanent junctional reciprocating tachycardia (PJRT) is a rare supraventricular tachycardia (SVT), typically involving a single decremental posteroseptal accessory pathway (AP). METHODS: Four patients with long RP SVT underwent electrophysiology (EP) study and ablation. The cases were reviewed. RESULTS: Case 1 recurred despite 3 prior ablations at the site of earliest retrograde atrial activation during orthodromic reciprocating tachycardia (ORT). Mapping during a repeat EP study demonstrated a prepotential in the coronary sinus (CS). Ablation over the earliest atrial activation in the CS resulted in dissociation of the potential from the atrium during sinus rhythm. The potential was traced back to the CS os and ablated. Case 2 underwent successful ablation at 6 o'clock on the mitral annulus (MA). ORT recurred and successful ablation was performed at 1 o'clock on the MA. Case 3 had tachycardia with variation in both V-A and A-H intervals which precluded the use of usual maneuvers so we used simultaneous atrial and ventricular pacing and introduced a premature atrial contraction with a closely coupled premature ventricular contraction. Case 4 had had two prior atrial fibrillation ablations with continued SVT over a decremental atrioventricular bypass tract that was successfully ablated at 5 o'clock on the tricuspid annulus. A second SVT consistent with a concealed nodoventricular pathway was successfully ablated at the right inferior extension of the AV nodal slow pathway. CONCLUSION: We describe challenging cases of PJRT by virtue of complex anatomy, diagnostic features, and multiple arrhythmia mechanisms.

Frequent Ventricular Ectopy: Implications and Outcomes.

Frequent ventricular ectopy is a common clinical presentation in patients suffering idiopathic ventricular outflow tract arrhythmias. These are focal arrhythmias that generally occur in patients without structural heart disease and share a predilection for characteristic anatomic sites of origin. Mechanistically, they are generally due to cyclic adenosine monophosphate (cAMP)-mediated triggered activity. As a result, there is typically an exercise or catecholamine related mode of induction and often a sensitivity to suppression with adenosine. Treatment options include clinical surveillance, medical therapy with anti-arrhythmic agents or catheter ablation. Medical therapy may offer symptomatic benefit but may have side-effects and usually results in burden reduction rather than eradication of ectopy. Catheter ablation using contemporary mapping techniques, whilst associated with some inherent procedural risk, is a potentially curative and safe option in most patients. Although usually associated with a good prognosis, some patients may develop an ectopy-mediated cardiomyopathy or, rarely, ectopy-induced polymorphic ventricular arrhythmias; catheter ablation is the treatment of choice in those patients.

Surface ECG and intracardiac spectral measures predict atrial fibrillation recurrence after catheter ablation.

INTRODUCTION: Outcome of patients undergoing catheter ablation of atrial fibrillation (AF) varies widely. We sought to investigate whether parameters derived from the spectral analysis of surface ECG and intracardiac AF electrograms can predict outcome in patients referred for pulmonary vein isolation (PVI). METHODS: We performed spectral analysis on the surface ECG and intracardiac electrograms from patients referred for AF ablation. After filtering and QRST subtraction, we measured the dominant frequency (DF), regularity index (RI) and the organizational index (OI) of fibrillatory electrograms and determined their value for predicting AF recurrence after ablation. A subjective, blinded prediction based on the surface ECG was also performed. RESULTS: We analyzed data from 153 PVI procedures in 140 patients (67.1% with persistent or longstanding AF). In a multivariable model, DF in the right atrium (RA) and distal coronary sinus (CSd)-to-RA DF gradient predicted AF recurrence (OR, 3.52, P = 0.023 and OR, 0.2, P = 0.034, respectively). DF in RA and CSd to RA DF gradient had a good predictive value for PVI outcome (area under the curve [AUC] of 0.73, P = 0.007 and 0.74, P = 0.007, respectively). These performed better than the subjective predictions of experienced electrophysiologists ( P = 0.2). CONCLUSIONS: Higher RA DF, lower CSd to RA DF gradient predicted recurrence after AF ablation. These spectral measures suggest a more remodeled atrial substrate and may provide simple tools for risk stratification or predict the need for additional substrate modification in patients referred for AF ablation.

Angiotensin converting enzyme 2 activity and human atrial fibrillation: increased plasma angiotensin converting enzyme 2 activity is associated with atrial fibrillation and more advanced left atrial structural remodelling.

AIM: Angiotensin converting enzyme 2 (ACE2) is an integral membrane protein whose main action is to degrade angiotensin II. Plasma ACE2 activity is increased in various cardiovascular diseases. We aimed to determine the relationship between plasma ACE2 activity and human atrial fibrillation (AF), and in particular its relationship to left atrial (LA) structural remodelling. METHODS AND RESULTS: One hundred and three participants from a tertiary arrhythmia centre, including 58 with paroxysmal AF (PAF), 20 with persistent AF (PersAF), and 25 controls, underwent clinical evaluation, echocardiographic analysis, and measurement of plasma ACE2 activity. A subgroup of 20 participants underwent invasive LA electroanatomic mapping. Plasma ACE2 activity levels were increased in AF [control 13.3 (9.5-22.3) pmol/min/mL; PAF 16.9 (9.7-27.3) pmol/min/mL; PersAF 22.8 (13.7-33.4) pmol/min/mL, P = 0.006]. Elevated plasma ACE2 was associated with older age, male gender, hypertension and vascular disease, elevated left ventricular (LV) mass, impaired LV diastolic function and advanced atrial disease (P < 0.05 for all). Independent predictors of elevated plasma ACE2 activity were AF (P = 0.04) and vascular disease (P < 0.01). There was a significant relationship between elevated ACE2 activity and low mean LA bipolar voltage (adjusted R2 = 0.22, P = 0.03), a high proportion of complex fractionated electrograms (R2 = 0.32, P = 0.009) and a long LA activation time (R2 = 0.20, P = 0.04). CONCLUSION: Plasma ACE2 activity is elevated in human AF. Both AF and vascular disease predict elevated plasma ACE2 activity, and elevated plasma ACE2 is significantly associated with more advanced LA structural remodelling.

Isolation of the posterior left atrium for patients with persistent atrial fibrillation: routine adenosine challenge for dormant posterior left atrial conduction improves long-term outcome.

AIMS: Catheter ablation to achieve posterior left atrial wall (PW) isolation may be performed as an adjunct to pulmonary vein isolation (PVI) in patients with persistent atrial fibrillation (AF). We aimed to determine whether routine adenosine challenge for dormant posterior wall conduction improved long-term outcome. METHODS AND RESULTS: A total of 161 patients with persistent AF (mean age 59 ± 9 years, AF duration 6 ± 5 years) underwent catheter ablation involving circumferential PVI followed by PW isolation. Posterior left atrial wall isolation was performed with a roof and inferior wall line with the endpoint of bidirectional block. In 54 patients, adenosine 15 mg was sequentially administered to assess reconnection of the pulmonary veins and PW. Sites of transient reconnection were ablated and adenosine was repeated until no further reconnection was present. Holter monitoring was performed at 6 and 12 months to assess for arrhythmia recurrence. Posterior left atrial wall isolation was successfully achieved in 91% of 161 patients (procedure duration 191 ± 49 min, mean RF time 40 ± 19 min). Adenosine-induced reconnection of the PW was demonstrated in 17%. The single procedure freedom from recurrent atrial arrhythmia was superior in the adenosine challenge group (65%) vs. no adenosine challenge (40%, P < 0.01) at a mean follow-up of 19 ± 8 months. After multiple procedures, there was significantly improved freedom from AF between patients with vs. without adenosine PW challenge (85 vs. 65%, P = 0.01). CONCLUSION: Posterior left atrial wall isolation in addition to PVI is a readily achievable ablation strategy in patients with persistent AF. Routine adenosine challenge for dormant posterior wall conduction was associated with an improvement in the success of catheter ablation for persistent AF.

A minimal or maximal ablation strategy to achieve pulmonary vein isolation for paroxysmal atrial fibrillation: a prospective multi-centre randomized controlled trial (the Minimax study).

AIMS: Pulmonary vein isolation (PVI) is the cornerstone of catheter ablation of atrial fibrillation (AF). The intervenous ridge (IVR) may be incorporated into ablation strategies to achieve PVI; however, randomized trials are lacking. We performed a randomized multi-centre international study to compare the outcomes of (i) circumferential antral PVI (CPVI) alone (minimal) vs. (ii) CPVI with IVR ablation to achieve individual PVI (maximal). METHODS AND RESULTS: Two hundred and thirty-four patients with paroxysmal AF underwent CPVI and were randomized to a minimal or maximal ablation strategy. The primary outcome of recurrent atrial arrhythmia was assessed with 7-day Holter monitoring at 6 and 12 months. PVI was achieved in all patients. Radiofrequency ablation time was longer in the maximal group (46.6 ± 14.6 vs. 41.5 ± 13.1 min; P < 0.01), with no significant differences in procedural or fluoroscopy times. At mean follow-up of 17 ± 8 months, there was no difference in freedom from AF after a single procedure between a minimal (70%) and maximal ablation strategy (62%; P = 0.25). In the minimal group, ablation was required on the IVR to achieve electrical isolation in 44%, and was associated with a significant reduction in freedom from AF (57%) compared with the minimal group without IVR ablation (80%; P < 0.01). CONCLUSION: There was no statistically significant difference in freedom from AF between a minimal and maximal ablation strategy. Despite attempts to achieve PVI with antral ablation, IVR ablation is commonly required. Patients in whom antral isolation can be achieved without IVR ablation have higher long-term freedom from AF (the Minimax study; ACTRN12610000863033).

Absence of gender-based differences in the atrial and pulmonary vein substrate: a detailed electroanatomic mapping study.

BACKGROUND: Gender-based differences in the clinical nature of cardiac arrhythmias such as atrial fibrillation (AF) are well established. OBJECTIVE: The purpose of this study was to identify any such gender-based differences in the underlying pulmonary vein and atrial substrate. METHODS AND RESULTS: Thirty-eight patients with no history of AF undergoing catheter ablation for supraventricular tachycardia (SVT) and 55 with paroxysmal or persistent AF undergoing catheter ablation of AF underwent detailed electroanatomic mapping of the pulmonary veins and atria. Refractory periods in multiple locations, sinus node function, endocardial bipolar voltage, pulmonary vein and atrial conduction, and bipolar electrogram complexity were analyzed. There were no significant between-gender differences in age or other clinical variables known to impact on the atrial or pulmonary vein substrate. In neither the AF nor the non-AF cohorts were there any significant differences in atrial or pulmonary vein refractoriness, sinus node function, any measure of PV electrophysiology, or any measure of atrial electrophysiology. CONCLUSION: No systematic between-gender differences were observed in the PV or atrial substrate either in those with or without a history of AF, with a similar prevalence of the cardiovascular comorbidities frequently associated with atrial remodeling and AF seen in both male and female groups.

Ten-year trends in the use of catheter ablation for treatment of atrial fibrillation vs. the use of coronary intervention for the treatment of ischaemic heart disease in Australia.

AIMS: Percutaneous coronary intervention (PCI) and catheter ablation are well-accepted therapeutic interventions for treatment of coronary artery disease and atrial fibrillation (AF), respectively. We sought to examine temporal trends in the provision of these services over the past decade in Australia. METHODS AND RESULTS: A retrospective review of the numbers of PCIs and AF ablations from 2000/01 to 2009/10 was performed on data from three sources: the Australian Institute of Health, Welfare and Aging (AIHW), Medicare Australia database (MA), and local records at a high volume tertiary referral centre (RMH) for AF ablation. Linear regression models were fitted comparing trends in population-adjusted procedural numbers over the 10-year period. There was a 5% per year population-adjusted increment in PCIs over 10 years from both the AIHW and MA sources, respectively (P < 0.001). This was similar to the growth rate of all cardiovascular procedures (AIHW: 5.1 vs. 3.8%/year, P = 0.27). Atrial fibrillation ablations showed a 30.9, 23.2, and 39.8% per year population-adjusted increment over 10 years from the AIHW, MA, and RMH sources respectively (P < 0.001 for all). Growth of AF ablations was significantly higher than PCIs (P < 0.001 for AIHW and MA sources) and all cardiovascular procedures (AIHW: 30.9 vs. 3.8%/year, P < 0.001). CONCLUSION: The provision of catheter-based AF ablation services in Australia has increased exponentially over the past decade. Its annual growth rate exceeded that of PCIs and all cardiovascular procedures. Given the increasing epidemic of AF, these data have critical implications for public health policy assessing the adequacy of infrastructure, training, and funding for AF ablation services.

Update on the management of atrial fibrillation.

Atrial fibrillation (AF) is a common arrhythmia, with a prevalence that increases markedly with increasing age. Presence of AF has implications for management of future stroke risk. If the patient's pulse is irregular, an electrocardiogram should be ordered. Key management decisions are whether to adopt a rhythm control or a rate control strategy and whether to initiate anticoagulation. The primary aim of a rhythm control strategy is improved symptom control. AF ablation may be considered in younger patients (aged < 65 years) with paroxysmal or early persistent AF. AF increases the risk of stroke, and anticoagulation should be considered on the basis of stroke risk - clearly indicated with a CHADS 2 score (congestive heart failure, hypertension, age ≥ 75 years, diabetes, 1 point each; previous stroke or transient ischaemic attack, 2 points) of ≥ 2 - independent of the type of AF. In most patients with AF, the benefit of stroke reduction with systemic anticoagulation will outweigh its bleeding risks. All anticoagulants and antiplatelet agents increase the risk of bleeding. However, the new oral anticoagulants tend to have an improved safety profile, particularly in regard to intracranial bleeding, and are at least as effective as warfarin for stroke prevention.

Longitudinal risk of death, hospitalizations for atrial fibrillation, and cardiovascular events following catheter ablation of atrial fibrillation: a cohort study.

AIMS: Population studies reporting contemporary long-term outcomes following catheter ablation of atrial fibrillation (AF) are sparse.We evaluated long-term clinical outcomes following AF ablation and examined variation in outcomes by age, sex, and the presence of heart failure. METHODS AND RESULTS: We identified 30 601 unique patients (mean age 62.7 ± 11.8 years, 30.0% female) undergoing AF ablation from 2008 to 2017 in Australia and New Zealand using nationwide hospitalization data. The primary outcomes were all-cause mortality and rehospitalizations for AF or flutter, repeat AF ablation, and cardioversion. Secondary outcomes were rehospitalizations for other cardiovascular events. During 124 858.7 person-years of follow-up, 1900 patients died (incidence rate 1.5/100 person-years) with a survival probability of 93.0% (95% confidence interval (CI) 92.6-93.4%) by 5 years and 84.0% (95% CI 82.4-85.5%) by 10 years. Rehospitalizations for AF or flutter (13.3/100 person-years), repeat ablation (5.9/100 person-years), and cardioversion (4.5/100 person-years) were common, with respective cumulative incidence of 49.4% (95% CI 48.4-50.4%), 28.1% (95% CI 27.2-29.0%), and 24.4% (95% CI 21.5-27.5%) at 10 years post-ablation. Rehospitalizations for stroke (0.7/100 person-years), heart failure (1.1/100 person-years), acute myocardial infarction (0.4/100 person-years), syncope (0.6/100 person-years), other arrhythmias (2.5/100 person-years), and new cardiac device implantation (2.0/100 person-years) occurred less frequently. Elderly patients and those with comorbid heart failure had worse survival but were less likely to undergo repeat ablation, while long-term outcomes were comparable between the sexes. CONCLUSION: Patients undergoing AF ablations had good long-term survival, a low incidence of rehospitalizations for stroke or heart failure, and about half remained free of rehospitalizations for AF or flutter, including for repeat AF ablation, or cardioversion.

Impact of collimation on radiation exposure during interventional electrophysiology.

AIMS: Fluoroscopy remains a cornerstone imaging technique in contemporary electrophysiology practice. We evaluated the impact of collimation to the 'minimal required field size' on clinically significant parameters of radiation exposure. METHODS AND RESULTS: Radiation dose measured by dose area product (DAP) and radiation dose rate measured by DAP per minute of fluoroscopy were determined for all 571 electrophysiology procedures performed in a single electrophysiology laboratory from January 2010 to December 2010. Data from 205 procedures performed by one interventional electrophysiologist, who instituted a practice of routinely collimating to the minimum required visual fluoroscopy field on a case-by-case basis, were compared with data from 366 procedures performed by the three other experienced interventional electrophysiologists using the laboratory who continued their existing practice of ad hoc collimation. Significant reductions in radiation exposure were seen with the practice of routine maximal collimation. The largest reductions were seen during 'simple' ablation procedures. CONCLUSION: A practice of routinely collimating to the minimum required visual fluoroscopy field results in significant reductions in radiation exposure when compared with a usual approach to collimation. This may have important implications for risk of malignancy in patients and operators.

Radiofrequency ablation for atrial tachycardia and atrial flutter.

Atrial tachycardia is a generic term for a range of tachyarrhythmias with their origin in the atria. These can be broadly divided by mechanism into macro-reentrant, focal and small circuit re-entry. "Atrial flutter" is a term which, today, should be restricted to those classical circuits around the tricuspid annulus dependent on the cavo-tricuspid isthmus. The advent of sophisticated mapping solutions has rendered the vast majority of these atrial circuits curable with catheter ablation, with high success rates and very low incidence of complications.

Safety and Efficacy of Leadless Pacemakers: A Systematic Review and Meta-Analysis.

Background Leadless pacemaker is a novel technology, and evidence supporting its use is uncertain. We performed a systematic review and meta-analysis to examine the safety and efficacy of leadless pacemakers implanted in the right ventricle. Methods and Results We searched PubMed and Embase for studies published before June 6, 2020. The primary safety outcome was major complications, whereas the primary efficacy end point was acceptable pacing capture threshold (≤2 V). Pooled estimates were calculated using the Freedman-Tukey double arcsine transformation. Of 1281 records screened, we identified 36 observational studies of Nanostim and Micra leadless pacemakers, with most (69.4%) reporting outcomes for the Micra. For Micra, the pooled incidence of complications at 90 days (n=1608) was 0.46% (95% CI, 0.08%-1.05%) and at 1 year (n=3194) was 1.77% (95% CI, 0.76%-3.07%). In 5 studies with up to 1-year follow-up, Micra was associated with 51% lower odds of complications compared with transvenous pacemakers (3.30% versus 7.43%; odds ratio [OR], 0.49; 95% CI, 0.34-0.70). At 1 year, 98.96% (95% CI, 97.26%-99.94%) of 1376 patients implanted with Micra had good pacing capture thresholds. For Nanostim, the reported complication incidence ranged from 6.06% to 23.54% at 90 days and 5.33% to 6.67% at 1 year, with 90% to 100% having good pacing capture thresholds at 1 year (pooled result not estimated because of the low number of studies). Conclusions Most studies report outcomes for the Micra, which is associated with a low risk of complications and good electrical performance up to 1-year after implantation. Further data from randomized controlled trials are needed to support the widespread adoption of these devices in clinical practice.

The Role of the Left Septal Fascicle in Fascicular Arrhythmias: Clinical Presentation and Laboratory Evaluation.

OBJECTIVES: This study describes a series of cases best explained by invoking the left septal fascicle (LSF) as a critical component of the arrhythmia circuit. BACKGROUND: Numerous anatomic studies have shown evidence of the LSF, but its precise role in the onset of arrhythmia is unclear. METHODS: This paper presents 5 cases that implicated the LSF as a critical component of arrhythmogenesis. RESULTS: The first case had ventricular fibrillation repeatedly documented after a single premature atrial complex, produced left-sided conduction delay and simultaneous earliest activation of the left anterior fascicle (LAF) and left posterior fascicle (LPF). The LSF was ablated, resulting in an arrhythmia cure. The second case showed narrow QRS morphology during fascicular re-entrant tachycardia. The earliest mid-septal diastolic potentials had distal-to-proximal activation suggesting an LSF as a retrograde common pathway. The third case, with multiple ectopic Purkinje-related premature complexes exhibited earliest Purkinje potentials in the mid-septum, with subsequent anterograde activation of the LAF and LPF. Ablation of the LSF eliminated the premature ventricular complexes (PVCs). The fourth case demonstrated LPF and LAF PVCs. The His-left bundle activation showed earliest potentials at the proximal insertion of the left bundle during LPF PVCs, as well as a distal-to-proximal activation pattern during LAF PVC, suggestive of LSF involvement. The fifth case had focal non-re-entrant fascicular beats successfully ablated over the LSF. CONCLUSIONS: Involvement of the LSF is suspected with presentation of multiform fascicular and narrow QRS complex ventricular episodes of arrhythmia. Diagnoses and ablation require detailed mapping of the entire left sided conduction system.

A Randomized, Double-Blind, Placebo-Controlled Trial of Intravenous Alcohol to Assess Changes in Atrial Electrophysiology.

OBJECTIVES: This study sought to identify acute changes in human atrial electrophysiology during alcohol exposure. BACKGROUND: The mechanism by which a discrete episode of atrial fibrillation (AF) occurs remains unknown. Alcohol appears to increase the risk for AF, providing an opportunity to study electrophysiologic effects that may render the heart prone to arrhythmia. METHODS: In this randomized, double-blinded, placebo-controlled trial, intravenous alcohol titrated to 0.08% blood alcohol concentration was compared with a volume and osmolarity-matched, masked, placebo in patients undergoing AF ablation procedures. Right, left, and pulmonary vein atrial effective refractory periods (AERPs) and conduction times were measured pre- and post-infusion. Isoproterenol infusions and burst atrial pacing were used to assess AF inducibility. RESULTS: Of 100 participants (50 in each group), placebo recipients were more likely to be diabetic (22% vs. 4%; p = 0.007) and to have undergone a prior AF ablation (36% vs. 22%; p = 0.005). Pulmonary vein AERPs decreased an average of 12 ms (95% confidence interval: 1 to 22 ms; p = 0.026) in the alcohol group, with no change in the placebo group (p = 0.98). Whereas no statistically significant differences in continuously assessed AERPs were observed, the proportion of AERP sites tested that decreased with alcohol (median: 0.5; interquartile range: 0.6 to 0.6) was larger than with placebo (median: 0.4; interquartile range: 0.2 to 0.6; p = 0.0043). No statistically significant differences in conduction times or in the proportion with inducible AF were observed. CONCLUSIONS: Acute exposure to alcohol reduces AERP, particularly in the pulmonary veins. These data demonstrate a direct mechanistic link between alcohol, a common lifestyle exposure, and immediate proarrhythmic effects in human atria. (How Alcohol Induces Atrial Tachyarrhythmias Study [HOLIDAY]; NCT01996943).

Standard peak-to-peak bipolar voltage amplitude criteria underestimate myocardial scar during substrate mapping with a novel microelectrode catheter.

BACKGROUND: Ventricular bipolar voltage values <0.5 and <1.0/1.5 mV (epi- and endocardium) correlating with dense scar and border zone, respectively, were established using a 3.5-mm tip catheter. Novel microelectrode catheters promise improved mapping resolution; however, whether standard voltage criteria apply to catheters with smaller electrode size and interelectrode distance remains unclear. OBJECTIVE: The purpose of this study was to determine whether traditional bipolar voltage criteria for scar apply during substrate mapping with a microelectrode catheter. METHODS: Paired bipolar and microbipolar voltage values were acquired from control swine (n = 2) using the microelectrode catheter and assessed for systemic differences. In a postinfarction swine model (n = 6), scar characteristics were compared between the bipolar maps and microbipolar maps using both standard and adjusted voltage criteria derived from the control animals. RESULTS: In control swine, although 5th percentile values for bipolar and microbipolar voltage were similar (1.12 vs 1.22 mV [left ventricular (LV) endo]; 0.88 mV vs 0.98 mV [epi]), median values were significantly greater when acquired by microbipolar electrodes (3.60 vs 6.76 mV, P = .002 [LV endo]; 2.61 vs 2.72 mV, P = .02 [epi]). Microbipolar values were systematically larger by 2.0× and 1.4× in the LV endocardium and epicardium, respectively. Application of standard voltage values to microbipolar maps in postinfarct swine underestimated scar area by approximately 41% in the LV endocardium (13.7 vs 33.4 cm2, P = .004). CONCLUSION: Bipolar voltage values acquired from microelectrodes are systemically larger than those acquired from standard catheters. New reference values should be established for these novel catheters.

Site-Specific Epicardium-to-Endocardium Dissociation of Electrical Activation in a Swine Model of Atrial Fibrillation.

OBJECTIVES: This study sought to define the extent and spatial distribution of endocardial-epicardial dissociation (EED) in a swine model. BACKGROUND: The mechanisms underlying persistent atrial fibrillation (AF) remain unclear. METHODS: Sixteen swine underwent simultaneous endocardial and epicardial mapping using 32-electrode grid catheters. This included 6 swine with rapid atrial pacing-induced atrial remodeling. Three right atrial (RA) and 3 left atrial (LA) regions were mapped during sinus rhythm, atrial pacing, acute or persistent AF, and AF in the presence of pericardial acetylcholine. Unipolar electrogram recordings over 10-s epochs underwent offline phase analysis using customized software. Regional activation patterns on paired surfaces and the instantaneous phase at each matched electrode location were analyzed. EED was defined as paired electrodes out of phase by ≥20 ms. RESULTS: The mean distance between matched endocardial-epicardial electrode pairs was 4.4 ± 1.8 mm. During episodes of AF, rotational activations with ≥3 full rotations were not seen. EED was seen during 34.4 ± 16.4% of mapped time periods: LA > RA, persistent > acute AF in the LA, and acetylcholine-induced > acute AF in both atria (p < 0.05 for each). Most marked EED in persistent AF was in the LA appendage (47.2 ± 3.7%) and the LA posterior wall (50.3 ± 4.7%). CONCLUSIONS: Marked EED was seen in a swine model of AF, particularly during persistent AF. There was significantly more EED in the LA than the RA and, particularly, in the LA PW and LAA. Mapping approaches limited to the endocardium may not sufficiently characterize the complexity of AF.

Dyssynchrony and Fibrosis Persist After Resolution of Cardiomyopathy in a Swine Premature Ventricular Contraction Model.

OBJECTIVES: This study sought to prospectively study the development and then regression of premature ventricular contraction (PVC)-induced cardiomyopathy, with the hypothesis that structural left ventricular (LV) changes that are of potential clinical significance may endure beyond the period of exposure to PVCs. BACKGROUND: Recovery of LV function after eradication of PVCs in PVC-induced cardiomyopathy is incompletely defined. METHODS: Fifteen swine were exposed to: 1) 50% paced PVCs from the LV lateral epicardium for 12 weeks (LV PVC, n = 5); 2) no pacing for 12 weeks (Control, n = 5); or 3) 50% paced LV PVCs for 12 weeks followed by pacing cessation for 4 weeks (Recovery, n = 5). LV function was quantified biweekly in sinus rhythm with echocardiography. Dyssynchrony was measured from pressure-volume loops at baseline and terminal studies. LV fibrosis was quantified after sacrifice. RESULTS: LV ejection fraction during sinus rhythm fell between baseline and terminal studies in the LV PVC group (65.8 ± 3.0 to 39.3 ± 3.2; p < 0.05), whereas there was no significant change in the Control group (69.6 ± 3.0 to 72.2 ± 3.0; p = NS) or after Recovery (64.5 ± 3.4% to 61.4 ± 3.4%; p = NS) groups. There was a significant increase in LV dyssynchrony measured during sinus rhythm between baseline and terminal studies in the LV PVC group (4.0 ± 1.5% to 9.0 ± 1.5%; p < 0.05); there was a similar increase in dyssynchrony that persisted 4 weeks after PVC cessation in the Recovery group (4.4 ± 1.7% to 12.8 ± 1.7%; p < 0.05). After sacrifice, percent fibrosis was higher in the LV PVC group compared with Control (5.7 ± 0.3% vs. 3.0 ± 0.3%; p < 0.05) and remained elevated in Recovery (4.1 ± 0.3% vs. 3.0 ± 0.3%; p < 0.05) despite return to baseline LV ejection fraction. CONCLUSIONS: In a swine model of PVC-induced cardiomyopathy, cessation of PVCs for 4 weeks leads to normalization of LV systolic function but significant changes in myocardial fibrosis and LV dyssynchrony during sinus rhythm persist.

Endocardial-Epicardial Phase Mapping of Prolonged Persistent Atrial Fibrillation Recordings: High Prevalence of Dissociated Activation Patterns.

BACKGROUND: Endocardial-epicardial dissociation and focal breakthroughs in humans with atrial fibrillation (AF) have been recently demonstrated using activation mapping of short 10-second AF segments. In the current study, we used simultaneous endo-epi phase mapping to characterize endo-epi activation patterns on long segments of human persistent AF. METHODS: Simultaneous intraoperative mapping of endo- and epicardial lateral right atrium wall was performed in patients with persistent AF using 2 high-density grid catheters (16 electrodes, 3 mm spacing). Filtered unipolar and bipolar electrograms of continuous 2-minute AF recordings and electrodes locations were exported for phase analyses. We defined endocardial-epicardial dissociation as phase difference of ≥20 ms between paired endo-epi electrodes. Wavefronts were classified as rotations, single wavefronts, focal waves, or disorganized activity as per standard criteria. Endo-Epi wavefront patterns were simultaneously compared on dynamic phase maps. Complex fractionated electrograms were defined as bipolar electrograms with ≥5 directional changes occupying at least 70% of sample duration. RESULTS: Fourteen patients with persistent AF undergoing cardiac surgery were included. Endocardial-epicardial dissociation was seen in 50.3% of phase maps with significant temporal heterogeneity. Disorganized activity (Endo: 41.3% versus Epi: 46.8%, P=0.0194) and single wavefronts (Endo: 31.3% versus Epi: 28.1%, P=0.129) were the dominant patterns. Transient rotations (Endo: 22% versus Epi: 19.2%, P=0.169; mean duration: 590±140 ms) and nonsustained focal waves (Endo: 1.2% versus Epi: 1.6%, P=0.669) were also observed. Apparent transmural migration of rotational activations (n=6) from the epi- to the endocardium was seen in 2 patients. Electrogram fractionation was significantly higher in the epicardium than endocardium (61.2% versus 51.6%, P<0.0001). CONCLUSIONS: Simultaneous endo-epi phase mapping of prolonged human persistent AF recordings shows significant Endocardial-epicardial dissociation marked temporal heterogeneity, discordant and transitioning wavefronts patterns and complex fractionations. No sustained focal activity was observed. Such complex 3-dimensional interactions provide insight into why endocardial mapping alone may not fully characterize the AF mechanism and why endocardial ablation may not be sufficient. Graphic Abstract: A graphic abstract is available for this article.