Months Of Atrial Fibrillation Research Articles

A surgical case of anti-coagulant ileus mimicking small-bowel tumors: a case report

BackgroundAnti-coagulant ileus, characterized by intramural hematoma due to excessive anti-coagulant therapy, presents a diagnostic challenge. Although previously considered uncommon, recently, reporting cases of anti-coagulant ileus have become more frequent. Herein, we report a rare surgical case of anti-coagulant ileus mimicking small-bowel tumors.Case presentationA 79-year-old man was admitted to our hospital for fatigue. He had been administered warfarin for 5 months for atrial fibrillation. On admission, the patient exhibited mild epigastric tenderness. Laboratory test results revealed anemia (hemoglobin, 8.4 g/dL); unmeasurably prolonged prothrombin time (PT) with international normalized ratio (INR) > 8; and elevated soluble interleukin 2 receptor (sIL-2R) levels (849 IU/mL; normal range, 122–496 IU/mL). Abdominal plain computed tomography (CT) showed a circumferentially thickened intestinal wall at one site in the jejunum and two in the ileum. After hospitalization, bowel obstruction did not improve with conservative treatment. Suspecting small-bowel tumors such as lymphoma, the patient subsequently underwent open surgery on day 3 after admission. No obvious tumor mass was observed intra-operatively. However, only thickened and hemorrhagic segments were identified at the suspected sites. We performed partial jejunal and ileal resections of 12 and 27 cm, respectively. Histopathology confirmed submucosal congestion, edema, and hemorrhage in each area without tumor components, leading to the final diagnosis of intramural hematoma. The postoperative course was uneventful, and he was discharged on postoperative day 9. No recurrence occurred during the 5-year follow-up period.ConclusionsWe encountered a surgical case of anti-coagulant ileus, which was difficult to differentiate from malignant lymphoma based on CT findings and high sIL-2R levels. The possibility of anti-coagulant ileus should always be considered in patients on long-term anticoagulation medication and bowel obstruction with high PT-INR values.

P229 IMPROVED CLINICAL–INSTRUMENTAL OUTCOMES IN PATIENTS WITH CHRONIC DILATED HYPERTENSIVE / ISCHEMIC HEART DISEASE, UNDERGOING CCM, CARRIER OF CRTD WITH PERSISTENT SEVERE LEFT VENTRICULAR DYSFUNCTION

Abstract A 62–year–old man repeatedly subjected to PTCA + stent with severe left ventricular dysfunction and estimated FE 15%. After some hospitalizations for heart failure in 2015 he underwent an AICD implant Biventricular. Followed up in our clinics dedicated to heart failure, the patient did not present the characters of the CRT responder presenting a constant high end–systolic volume (224 ml) and none FE improvement of 15%. There was also an asthenia and tendency to inactivity and elevated NT Pro BNP levels despite optimal medical therapy even with entresto 24/26 mg x 2 / day. It has been decided to submit the patient enrolled in the cardiac transplant and / or VAD implantation lists to an implantation procedure of CCM system (cardiac contractility modulation). After two active fixation placement leads on the interventricular septum and connection to the CCM system housed in the subcutaneous pocket right contralateral to the biventricular AICD, the patient was monitored. We have noticed since the first days conditions of hemodynamic stability. Scheduled CCM therapy delivery for 10 hours a day. Following subsequently in the follow up at 3 – 6 – 12 – 18 months the patient showed an improvement of minneshota quality of life questionnaire in heart failure: MLWHFQ (44 at baseline, 17 at two months, 15 to six months, 10 to 12 months and 3 to 18 months), an increase in FE from 15 to 23 up to 26%, a reduction of the NTPROBNP from 13444 to 1178 then climbed back to 5549 and 3712 at 18 months for atrial fibrillation, without any requires re–hospitalization, an increased physical activity of the patient detected by the sensors of the two devices

Acute pericarditis after atrial fibrillation ablation: Incidence, characteristics, and risk factors

BackgroundLittle is known about the incidence and risk factors for the development of acute pericarditis after ablation for atrial fibrillation (AF).ObjectiveThe purpose of this retrospective cohort study was to describe the occurrence of and associations with suspected acute pericarditis after AF ablation.MethodsAll patients undergoing AF ablation in our center were enrolled in a prospectively maintained registry. Suspected acute pericarditis was defined as pericardial chest pain treated with disease specific anti-inflammatories within 3 months of AF ablation.ResultsAmong 2215 patients with AF ablations between January 1, 2018, and December 31, 2019, 226 (10.2%) had suspected acute pericarditis. Treatments included colchicine in 149 patients (65.9%), prednisone in 66 (29.2%), and high-dose ibuprofen in 43 (19.0%). Multiple anti-inflammatory therapies were used in 57 patients (25%). At baseline, a lower CHADS2VASc score and a higher body mass index were associated with pericarditis, whereas older patients were less likely to have pericarditis. With multivariable adjustment, age was associated with suspected acute pericarditis (odds ratio 0.95; 95% confidence interval 0.94–0.97; P <.0001). Among patients with suspected pericarditis, postprocedure pericardial effusion was present in 9.3% and pericarditis electrocardiographic changes in 19.5%.ConclusionSuspected acute pericarditis is common after AF ablation and is associated with a younger age. Systematic assessments for acute pericarditis after AF ablation should be considered.

B-PO05-139 CHANGES IN FLOW DYNAMICS DUE TO PERSISTENT ATRIAL FIBRILLATION IN A CHRONICALLY PACED CANINE MODEL

Atrial Fibrillation (AF) increases the risk of stroke, presumably because poor left atrial (LA) contraction leads to impaired blood flow and the potential for clots to form. Previous studies have not looked at flow changes over the course of AF progression. We characterized longitudinal changes in blood flow dynamics in the LA due to sustained AF using 4D flow phase-contrast MRI. A chronically, rapidly paced canine model (n=3) was used for this study. MRI studies were performed on a 3T Prisma (Siemens) scanner in sinus rhythm: before AF induction and after 6 months of sustained AF. The 4D flow MRI used a velocity sensitivity of 150 cm/s and was corrected for Maxwell terms, velocity aliasing, and eddy currents. The LA chamber was segmented and divided into regions (pulmonary veins, LA appendage, and LA body). Peak velocity (5% of maximum velocity), stasis (relative number of voxels with speeds < 5 cm/s), and flow coherence (relative flow deviation) were analyzed. After 6 months of AF, peak velocity throughout the LA decreased (25.1 ± 1.1 cm/s to 20.8 ± 4.4 cm/s) and stasis increased (23.9 ± 3.9% to 32.3 ± 6.5%). The LA appendage experienced the greatest increase in stasis (25.6% at baseline to 35.1% after AF, a 37.1% change) and had a 15.8% decrease in peak velocity (19.8 cm/s at baseline to 16.7 cm/s after AF). Flow coherence after AF decreased throughout the LA (12% greater deviation) with the greatest decrease in the LA body (14.3% greater deviation). AF negatively affects blood flow dynamics leading to increased stasis and decreased flow coherence in the LA. These factors may contribute to the increased risks of clot formation in AF patients.

B-PO02-030 ELECTROPHYSIOLOGICAL CHANGES IN PERSISTENT ATRIAL FIBRILLATION IN A CHRONICALLY PACED CANINE MODEL

Previous studies have described slowly conducting regions in patients experiencing atrial fibrillation (AF). However, no studies have shown changes in conduction as AF progresses. We investigated the conduction changes that occur during the progression of AF in a canine model and relate them to the underlying substrate remodeling. High-density electrophysiological (EP) studies were performed on a chronically, rapidly paced canine model (n=10) using an Orion catheter and the Rhythmia (Boston Scientific) cardiac mapping system. Substrate information came from LGE MRI performed on a 3T Prisma (Siemens) scanner. Both EP and MRI procedures were performed before AF induction and repeated after 6 months of AF. Left atrial activation times were mapped in sinus rhythm and registered onto the MRI geometry. Conduction velocity was calculated using a triangulation-based approach. Left atrial wall fibrosis was characterized using normalized intensity (NI). Overall conduction speed decreased after sustained AF (1.32 ± 0.43 m/s at baseline to 1.14 ± 0.32 m/s after 6 months of AF, p<0.01). The speed decrease was larger in areas that developed fibrosis compared to the healthy region (0.23m/s vs. 0.14m/s, p<0.01) with a correlation of 0.015 m/s decrease per NI unit increase. The conduction direction changed by a mean of 54 degrees. Conduction changes in both magnitude and direction occur in areas of increased fibrosis, supporting the theory that structural remodeling plays a role in AF development and sustainability. These changes could contribute to making AF sustain beyond pulmonary vein triggers as it progresses from paroxysmal to persistent.

Changes in atrial electrophysiological and structural substrate and their relationship to histology in a long-term chronic canine atrial fibrillation model.

Atrial fibrillation (AF) is related to numerous electrophysiological changes; however, the extent of structural and electrophysiological remodeling with long-term AF is not well characterized. Dogs (n=6) were implanted with a neurostimulator in the right atrium (AF group). No implantation was done in the Control group (n=3). Electroanatomical mapping was done prior to and following more than 6 months of AF. Magnetic resonance imaging was also done to assess structural remodeling. Animals were euthanized and tissue samples were acquired for histological analysis. A significant increase was seen in the left atrial (LA) volume among all AF animals (22.25 ± 12.60 cm3 vs 34.00 ± 12.23 cm3 , P=.01). Also, mean bipolar amplitude in the LA significantly decreased from 5.96 ± 2.17mV at baseline to 3.23 ± 1.51mV (P<.01) after chronic AF. Those significant changes occurred in each anterior, lateral, posterior, septal, and roof regions as well. Additionally, the dominant frequency (DF) in the LA increased from 7.02 ± 0.37Hz to 10.12 ± 0.28Hz at chronic AF (P<.01). Moreover, the percentage of fibrosis in chronic AF animals was significantly larger than that of control animals in each location (P<.01). Canine chronic AF is accompanied by a significant decrease in intracardiac bipolar amplitudes. These decreased electrogram amplitude values are still higher than traditional cut-off values used for diseased myocardial tissue. Despite these "normal" bipolar amplitudes, there is a significant increase in DF and tissue fibrosis.

Effect of Catheter Ablation vs Antiarrhythmic Medication on Quality of Life in Patients With Atrial Fibrillation

Quality of life is not a standard primary outcome in ablation trials, even though symptoms drive the indication. To assess quality of life with catheter ablation vs antiarrhythmic medication at 12 months in patients with atrial fibrillation. Randomized clinical trial at 4 university hospitals in Sweden and 1 in Finland of 155 patients aged 30-70 years with more than 6 months of atrial fibrillation and treatment failure with 1 antiarrhythmic drug or β-blocker, with 4-year follow-up. Study dates were July 2008-September 2017. Major exclusions were ejection fraction <35%, left atrial diameter >60 mm, ventricular pacing dependency, and previous ablation. Pulmonary vein isolation ablation (n = 79) or previously untested antiarrhythmic drugs (n = 76). Primary outcome was the General Health subscale score (Medical Outcomes Study 36-Item Short-Form Health Survey) at baseline and 12 months, assessed unblinded (range, 0 [worst] to 100 [best]). There were 26 secondary outcomes, including atrial fibrillation burden (% of time) from baseline to 12 months, measured by implantable cardiac monitors. The first 3 months were excluded from rhythm analysis. Among 155 randomized patients (mean age, 56.1 years; 22.6% women), 97% completed the trial. Of 79 patients randomized to receive ablation, 75 underwent ablation, including 2 who crossed over to medication and 14 who underwent repeated ablation procedures. Of 76 patients randomized to receive antiarrhythmic medication, 74 received it, including 8 who crossed over to ablation and 43 for whom the first drug used failed. General Health score increased from 61.8 to 73.9 points in the ablation group vs 62.7 to 65.4 points in the medication group (between-group difference, 8.9 points; 95% CI, 3.1-14.7; P = .003). Of 26 secondary end points, 5 were analyzed; 2 were null and 2 were statistically significant, including decrease in atrial fibrillation burden (from 24.9% to 5.5% in the ablation group vs 23.3% to 11.5% in the medication group; difference -6.8% [95% CI, -12.9% to -0.7%]; P = .03). Of the Health Survey subscales, 5 of 7 improved significantly. Most common adverse events were urosepsis (5.1%) in the ablation group and atrial tachycardia (3.9%) in the medication group. Among patients with symptomatic atrial fibrillation despite use of antiarrhythmic medication, the improvement in quality of life at 12 months was greater for those treated with catheter ablation compared with antiarrhythmic medication. Although the study was limited by absence of blinding, catheter ablation may offer an advantage for quality of life. clinicaltrialsregister.eu Identifier: 2008-001384-11.

Atrial fibrillation observed on surface ECG can be atrial flutter or atrial tachycardia

BackgroundDifferentiating between atrial fibrillation (AF) and atrial tachycardia (AT) or atrial flutter (AFL) on surface ECG can be challenging. The same problem arises in animal models of AF, in which atrial arrhythmias are induced by pacing or pharmacological intervention with the goal of making mechanistic determinations. Some of these induced arrhythmias can be AFL or AT, even though it might appear as AF on the body-surface ECG based on irregular R-R intervals. We hypothesize that a dominant frequency (DF) analysis of the ECG can differentiate between the two distinct arrhythmias, even when it is not evident by the presence of flutter waves or beat-to-beat regularity when looking at brief recordings. MethodsCanine model (n = 15, 10 controls and 5 Persistent AF animals with >6 months of AF) was used to test the hypothesis. Atrial arrhythmia was induced by rapid atrial pacing. Five blinded observers evaluated the 3‑lead surface ECGs recorded during atrial arrhythmia and classified the rhythm as AFL/AT or AF. The 64-electrode Constellation (Boston Scientific) catheter was used to acquire left (entire group) and right (7 of 10 controls) atrial intracardiac electrograms. For the surface ECG and the intracardiac electrograms, Welch method with a hamming window and 50% overlap was used to calculate DF of two-minute segments. Mean of standard deviations of the DF values were calculated for both ECGs and intracardiac EGMs. Ground truth came from activations maps and DF analysis derived from the intracardiac electrograms recorded in the two chambers. ResultsRapid pacing induced atrial arrhythmias in all the control animals. The ECG in 8 of the 10 control cases was read as AF by at least 80% percent of observers even though the EGMs from the Constellation showed organized activation and consistent DF (STD of DF < 0.001) in all the electrodes confirming the arrhythmia as AFL in 10/10 cases. In the persistent AF group, the DF from the three lead ECGs were significantly different (Mean of STDs = 2.65 ± 0.99) whereas the DF in the control animals with AFL was consistent across all ECG channels (Mean of STDs < 0.001), and the DF in the control animals ECGs was in agreement with the DF of the intracardiac electrograms. ConclusionSurface ECG recordings can mimic AF even when the underlying atrial arrhythmia is AFL in control canine models. DF variation of the signals from multiple surface ECG leads can help differentiate between the AF and AFL.

Effect of induced chronic atrial fibrillation on exercise performance in Standardbred trotters.

BackgroundAtrial fibrillation (AF) is the most common arrhythmia affecting performance in horses. However, no previous studies have quantified the performance reduction in horses suffering from AF.ObjectivesTo quantify the effect of AF on maximum velocity (V max), maximum heart rate (HRmax), heart rate recovery (T 100), hematologic parameters and development of abnormal QRS complexes.AnimalsNine Standardbred trotters.MethodsTwo‐arm controlled trial. Six horses had AF induced by means of a pacemaker and 3 served as sham‐operated controls. All horses were subjected to an exercise test to fatigue before (SET1) and after (SET2) 2 months of AF or sham. The V max and HRmax were assessed using a linear mixed normal model. Abnormal QRS complexes were counted manually on surface ECGs.ResultsAtrial fibrillation resulted in a 1.56 m/sec decrease in V max (P < .0001). In the AF group, HRmax ± SD increased from 226 ± 11 bpm at SET1 to 311 ± 27 bpm at SET 2. The AF group had higher HRmax at SET2 compared with controls (P < .0001), whereas no difference between the control and AF groups was observed at SET1 (P = .96). Several episodes of wide complex tachycardia were observed during exercise in 3 of the AF horses during SET2.Conclusions and Clinical ImportanceAtrial fibrillation resulted in a significant reduction in performance, an increase in HR and development of abnormal QRS complexes during exercise, which may be a risk factor for collapse or sudden cardiac death.

Warfarin Safety: A Cross-Sectional Study of the Factors Associated with the Consumption of Medicinal Plants in a Brazilian Anticoagulation Clinic.

The aim of this study was to analyze factors associated with the consumption of medicinal plants by patients being treated with warfarin in a Brazilian anticoagulation clinic and to study the safety of medicinal plant use in patients on warfarin therapy. The study was performed as an observational cross-sectional analysis. Study participants were outpatients on long-term warfarin therapy for at least 2months for atrial fibrillation or prosthetic cardiac valves. Interviews were carried out concerning information about the habits of medicinal herb consumption, and logistic regression analysis was performed to identify factors associated with the consumption of herbs. The scientific names of the medicinal plants were identified to search for information on the effects on the hemostasis of the interactions between the medicinal herbs reported and warfarin. The mean age of the 273 patients included was 60.8years; 58.7% were women. Medicinal plants were used by 67% of the participants. No association between demographic and clinical data and the use of medicinal plants was identified. Patients reported a total of 64 different plants, primarily consumed in the form of tea. The plants were mainly used to treat respiratory tract and central nervous system disorders. About 40% of the plants cited have been reported to potentially interfere with the anticoagulation therapy, principally by potentiating the effects of warfarin, which could, increase the risk of bleeding. The use of medicinal plants was highly common and widespread in patients receiving warfarin as an anticoagulation therapy. Univariate analysis of variables associated with the consumption of herbs showed no statistically significant difference in the consumption of medicinal plants for any of the sociodemographic and clinical data. The medicinal plants that were reportedly consumed by the patients could affect hemostasis. This study reinforces the need for further studies evaluating the habits of patients consuming medicinal plants and their clinical implications, and will help to design strategies to manage the risks associated with warfarin-herbal interactions.

Progression of atrial remodeling in patients with high-burden atrial fibrillation: Implications for early ablative intervention

Advanced atrial remodeling predicts poor clinical outcomes in human atrial fibrillation (AF). The purpose of this study was to define the magnitude and predictors of change in left atrial (LA) structural remodeling over 12 months of AF. Thirty-eight patients with paroxysmal AF managed medically (group 1), 20 undergoing AF ablation (group 2), and 25 control patients with no AF history (group 3) prospectively underwent echocardiographic assessment of strain variables of LA reservoir function at baseline and at 4, 8, and 12 months. In addition, P-wave duration (Pmax,, Pmean) and dispersion (Pdis) were measured. AF burden was quantified by implanted recorders. Twenty patients undergoing ablation underwent electroanatomic mapping (mean 333 ± 40 points) for correlation with LA strain. Group 1 demonstrated significant deterioration in total LA strain (26.3% ± 1.2% to 21.7% ± 1.2%, P < .05) and increases in Pmax (132 ± 3 ms to 138 ± 3 ms, P < .05) and Pdis (37 ± 2 ms to 42 ± 2 ms, P < .05). AF burden ≥10% was specifically associated with decline in strain and with P-wave prolongation. Conversely, group 2 manifest improvement in total LA strain (21.3% ± 1.7% to 28.6% ± 1.7%, P <.05) and reductions in Pmax (136 ± 4 ms to 119 ± 4 ms, P < .05) and Pdis (47 ± 3 ms to 32 ± 3 ms, P < .05). Change was not significant in group 3. LA mean voltage (r = 0.71, P = .0005), percent low voltage electrograms (r = -0.59, P = .006), percent complex electrograms (r = -0.68, P = .0009), and LA activation time (r = -0.69, P = .001) correlated with total strain as a measure of LA reservoir function. High-burden AF is associated with progressive LA structural remodeling. In contrast, AF ablation results in significant reverse remodeling. These data may have implications for timing of ablative intervention.

Edema Bilateral do Disco Óptico Secundário a Amiodarona: Manifestação de uma Neuropatia Óptica Iatrogénica

A 69-years-old male patient was treated with amiodarone 200mg/day over the passed two months for atrial fibrillation. He presented a sudden, painless and unilateral visual loss. Ophthalmologic evaluation revealed a bilateral optic disc edema. Neurological examination was otherwise unremarkable. After properly excluding increased intracranial pressure and giant cell arteritis, the main differential diagnosis was between nonarteritic anterior ischemic optic neuropathy and optic neuropathy secondary to amiodarone. The latter diagnosis was favored due to a presence of bilateral and simultaneous optic disc edema, gradual improvement of symptoms after discontinuation of the drug, and, mostly, by persistence of optic disc edema beyond 6 weeks. Of note, an acute presentation of this disorder is common. Amiodarone optic neuropathy is a rare but potentially serious cause of optic nerve dysfunction, and its discontinuation is usually warrant.

Abstract 18832: High-Resolution, Whole Heart T1 Mapping in a Chronic Atrial Fibrillation Model

Introduction: Cardiac fibrosis is a marker of adverse remodeling of the heart. Cardiac T1 mapping is the only non-invasive method to assess diffuse myocardial fibrosis. However, existing T1 mapping techniques are not applicable for whole heart mapping with adequate spatial resolution to accurately evaluate the thin atrial wall. We have developed a novel, high-resolution, whole heart T1 mapping technique which can be used to characterize fibrosis in all cardiac chambers simultaneously. Methods: We applied the whole heart T1 mapping technique to study fibrosis progression in a canine, chronic atrial fibrillation (AF) model. Dogs (n=8) were subjected to rapid atrial pacing (RAP) and underwent baseline (n=8) and 8-month RAP MRIs (n=4) to evaluate myocardial fibrosis. Whole heart T1 mapping was performed on a 3 Tesla MRI scanner during slow contrast infusion (0.05 micromol/kg/sec of Gd-BOPTA). Spatial resolution of T1 mapping scans was 1.25x1.25x2.5 mm. T1 mapping was performed at least 30 minutes after start of slow contrast infusion to achieve steady-state for contrast distribution. Results: Figure 1a shows representative image of cardiac T1 maps that visualize the myocardium of all cardiac chambers clearly. Myocardium of LV and LA has similar T1 values in baseline scans (p=NS), which decreased significantly in the LV and LA 8 months after initialization of RAP (p&lt;0.05, Fig. 1b). This change in T1 indicates increased fibrosis of left ventricle and atrium after 8 months of AF. Conclusions: High-resolution, whole heart T1 mapping technique can be used to non-invasively assess diffuse myocardial fibrosis in all cardiac chambers. T1 mapping indicates that 8-months RAP results in increased LV and LA fibrosis.

Abstract 357: Effect of an Early Nurse Practitioner Based Transitional Care Program on Atrial Fibrillation Readmissions

Background: BRIDGE is a nurse practitioner (NP) based transitional care program for cardiac patients(pts) discharged from a large tertiary care health system. Attendance at the BRIDGE clinic has been shown to reduce early readmission and ED visits for acute coronary syndrome (ACS) pts. Little is known about causes of readmission for atrial fibrillation (AF) pts and whether an NP based program affects overall readmissions. Methods: Retrospective data on 1188 pts was abstracted from 2008 to 2010 for pts referred to BRIDGE. Early (30 day) readmission of pts with discharge diagnosis of AF underwent qualitative chart audit by a trained MD abstractor. When examining if BRIDGE affected readmissions, we excluded pts with ED visits/readmits prior to BRIDGE. Results: Median time to BRIDGE was 16 days. Of 1010 with complete data, 148 (15%) had a discharge diagnosis of AF; 110/148 (74%) AF pts attended BRIDGE. Thirty day readmission (30DR) for AF was 23% (34/148); 17/34 (57%) were sent to the ED by a MD or nurse. Attending BRIDGE had no effect on outcomes at all time points (table 1); 17 patients were readmitted before BRIDGE. Readmission at 6 months for AF was 41% for those who attended BRIDGE, 29% for those who did not (p=0.190). Table 2 details reasons for all 30DR in AF pts. Chart review demonstrated that all 30DR were appropriate, 83% (25/30) of non-elective readmissions were unavoidable, and of 5 potentially avoidable readmissions, 2 were due to patient non-compliance. Conclusions: 30-day readmission rates are high for pts recently discharged with a diagnosis of AF and most are unavoidable. A NP based transitional care clinic successful in reducing 30 day readmissions for ACS pts did not prevent either early or late readmissions in AF pts.

Transmural Conduction Is the Predominant Mechanism of Breakthrough During Atrial Fibrillation

Background— Endo-epicardial dissociation (EED) of electric activations resulting in transmural conduction of fibrillation waves (breakthroughs) has been postulated to contribute to the complexity of the substrate of atrial fibrillation (AF). The aim of this study was to elucidate the correlation between EED and incidence of breakthrough and to test the plausibility of transmural conduction versus ectopic focal discharges as sources of breakthrough. Methods and Results— We analyzed high-resolution simultaneous endo-epicardial in vivo mapping data recorded in left atrial free walls of goats with acute AF, 3 weeks and 6 months of AF (all n=7). Waves were analyzed for number, size, and width and categorized according to their origin outside (peripheral wave) or within the mapping area (breakthrough). Breakthrough incidence was lowest (2.1±1.0%) in acute AF, higher (11.4±6.1%) after 3 weeks ( P &lt;0.01 versus acute AF) and highest (14.2±3.8%) after 6 months AF ( P &lt;0.001 versus acute AF) and similar in the epicardium and endocardium. Most of the breakthroughs (86%; n=564) could be explained by transmural conduction, whereas only 13% (n=85) could be explained by ectopic focal discharges. Transmural microreentry did not play a role as source of breakthrough. Conclusions— This is the first study to present simultaneous endo-epicardial in vivo mapping data at sites of breakthrough events. Breakthrough incidence and degree of EED increased with increasing AF substrate complexity. In goat left atrial free walls, most of the breakthroughs can be explained by transmural conduction, whereas ectopic focal discharges play a limited role as source of breakthrough.

Loss of Continuity in the Thin Epicardial Layer Because of Endomysial Fibrosis Increases the Complexity of Atrial Fibrillatory Conduction

Background— The transition from persistent to permanent atrial fibrillation (AF) is associated with increased complexity of fibrillatory conduction. We have investigated the spatial distribution of fibrillation waves and structural alterations in the atrial free walls in a goat model of AF. Methods and Results— AF was maintained for 3 weeks (short term [ST], persistent AF) or 6 months (long term [LT], permanent AF). Fibrillation patterns were assessed with epicardial mapping. The origin of fibrillation waves and sites of conduction abnormalities were more homogeneously distributed in LT than in ST goats. Histologically, the total area fraction occupied by fibrous tissue and the degree of perimysial fibrosis (separation between myocyte bundles) were not significantly different between groups. However, endomysial fibrosis (distance between myocytes within bundles) was significantly larger in LT goats, particularly in the outer millimeter of the atria. By contrast, myocyte diameters were larger in LT goats throughout the atrial walls. High-resolution optical mapping showed that epicardial wavefront expansion was slower and more anisotropic in LT than in ST goats. Finally, a mathematical model of a simplified atrial architecture confirmed the potential impact of epicardial endomysial fibrosis on AF complexity. Conclusions— Altered propagation after 6 months of AF is consistent with homogeneous structural remodeling in the outer millimeter of the atria. Loss of continuity of the epicardial layer because of endomysial fibrosis may reduce its synchronizing effect, thereby increasing the complexity of fibrillatory conduction pathways. The exact distribution of fibrosis may be more important for the occurrence of conduction disturbances than the overall quantity.

Early Recurrence of Atrial Tachyarrhythmias Following Radiofrequency Catheter Ablation of Atrial Fibrillation

The use of blanking periods, the immediate period postablation during which transient tachyarrhythmia episodes are not considered recurrences, has been predicated on the assumption that not all early recurrences of atrial tachyarrhythmias (ERAT) will lead to later recurrences and, as such, does not necessarily represent treatment failure. While ERAT can be expected to occur in approximately 38% of patients within the first 3 months of atrial fibrillation (AF) ablation, only half of these patients will manifest later recurrences. Clinical features related to the patient's history of AF, the index ablation procedure, and particularities of the ERAT can help identify patients at higher risk of later recurrence in whom aggressive attempts to control rhythm, including early cardioversion and reintervention, may be justified.

Time course and mechanisms of endo-epicardial electrical dissociation during atrial fibrillation in the goat

This study aims to determine the degree and mechanisms of endo-epicardial dissociation of electrical activity during atrial fibrillation (AF) and endo-epicardial differences in atrial electrophysiology at different stages of atrial remodelling. Simultaneous high-density endo-epicardial mapping of AF was performed on left atrial free walls of goats with acute AF, after 3 weeks, and after 6 months of AF (all n = 7). Endo-epicardial activation time differences and differences in the direction of conduction vectors were calculated, endocardial and epicardial effective refractory periods (ERP) were determined, and fractionation of electrograms was quantified. Histograms of endo-epicardial activation time differences and differences in the direction of conduction vectors revealed two distinct populations, i.e. dissociated and non-dissociated activity. Dyssynchronous activity (dissociated in time) increased from 17 ± 7% during acute AF to 39 ± 17% after 3 weeks, and 68 ± 13% after 6 months of AF. Dissociation was more pronounced in thicker parts of the atrial wall (thick: 49.3 ± 21.4%, thin: 42.2 ± 19.0%, P < 0.05). At baseline, endocardial ERPs were longer when compared with epicardial ERPs (ΔERP, 21.8 ± 18 ms; P < 0.001). This difference was absent after 6 months of AF. The percentage of fractionated electrograms during rapid pacing increased from 9.4 ± 1.9% (baseline) to 18.6 ± 0.6% (6 months). During AF, pronounced dissociation of electrical activity occurs between the epicardial layer and the endocardial bundle network. The increase in dissociation is due to owing to progressive uncoupling between the epicardial layer and the endocardial bundles and correlates with increasing stability and complexity of the AF substrate.

Intracranial and fatal bleeding according to indication for long-term oral anticoagulant therapy.

Rate of major bleeding is generally accepted as a good measure of the risks associated with anticoagulant therapy, but this may not be true if the proportion of major bleeds with the most serious consequences differs according to the indication for anticoagulant therapy. To determine whether the indication for long-term oral anticoagulant therapy influences the proportion of major bleeds that are intracranial and fatal. Two authors abstracted intracranial and fatal bleeds from randomized trials of patients who received anticoagulant therapy for a minimum of 6months for atrial fibrillation, ischemic heart disease, venous thromboembolism, prosthetic heart valves and ischemic stroke. There were 877 major bleeds among 23,518 patients in 39 studies. The proportion of bleeds that were intracranial was significantly higher in patients with ischemic stroke (36%; 95% CI, 22-52%; P=0.02) compared with patients with venous thromboembolism (10%; 95% CI, 5-20%). The difference in the proportion of bleeds that were intracranial among atrial fibrillation, ischemic heart disease, venous thromboembolism and prosthetic heart valves was not statistically significant; however, the estimates varied from 10% to 27%. The proportion of bleeds that were fatal did not differ significantly according to indication, but varied from 8% to 20%. For all indications for anticoagulation, intracranial bleeds were much more likely to be fatal than extracranial major bleeds (44% vs. 4% overall). In current practise, the indication for oral anticoagulant therapy has limited influence on the proportion of major bleeds that are intracranial or fatal.

BAS/BSCR16 Time-dependent changes in atrial nitric oxide-redox balance in atrial fibrillation: translational research (from goats to humans)

RationaleOxidative stress has an important role in atrial fibrillation (AF)-induced myocardial remodelling, suggesting that specific oxidases may represent a novel therapeutic target in AF. Here we evaluated how the duration...