Abstract Background Contemporary guidelines recommend Catheter Ablation (CA) in patients with persistent Atrial Fibrillation (AF) with Heart Failure with reduced ejection fraction (HFrEF). It is challenging to prospectively predict who will respond. We have previously described the long-term survival outcomes of patients in this cohort.(1) However, the clinical characteristics associated with HF response and long-term clinical outcomes have not been reported. Objective To evaluate the association of HF parameters with cardiac functional response to CA and long-term survival after CA. Methods Post-hoc, long-term follow-up of mortality was undertaken in patients enrolled in the CAMTAF and ARC-HF RCTs. Both studies enrolled patients with persistent AF and HFrEF between 2005 and 2012 and randomised to first-time CA or medical therapy alone. Left ventricular ejection fraction (LVEF) and peak VO2 were measured in both studies at baseline and 12-month follow-up. The Universal Definition of HF response (LVEF improves by >10% points or to an LVEF >50%) was used.(2,3) Multi-variate logistic regression was used to determine features associated with HF response and Cox proportional hazards modelling for survival. Results 102 patients underwent randomisation with 52 assigned to CA. The mean age was 60.2 ±10.7 years with 93 (91.2%) male. The mean Baseline LVEF was 31 ±11% and peak VO2 was 1815 ±642mlmin-1. Baseline LVEF did not correlate significantly with Minnesota Living with Heart Failure (MLWHF) score (r=-0.11, p=0.29) whereas baseline peak VO2 did (r=-0.28, p<0.01). In patients randomised to CA, the median (IQR) improvement in LVEF was +8.4% (0, 15%). 22/52 (42.3%) patients were classified as Responders based on the Universal Criteria. Responders were younger (54.7 ±10.6 years vs 61.8 ±11.4, p=0.03) and had a higher mean HR on baseline Holter monitoring (89 ±14bpm vs 79 ±11bpm p<0.01) than non-responders. There was no significant difference in sex, baseline MLWHF scores, BNP levels or LVEF between groups (28±9% vs 31 ±9%, p=0.19). Responders had a significantly higher peak VO2 at baseline than Non-Responders (1972 ±668mlmin-1 vs 1556 ±580mlmin-1, p=0.03). On multivariate analysis, mean heart rate on Holter monitoring and peak VO2 were significantly associated with Responder status post-ablation. (Table 1a) During a median follow-up of 7.8 (3.9 –9.9) years, 34 (33.3%) patients died, including 17 (32.7%) patients in the CA arm. On univariate analysis, baseline peak VO2 was significantly greater of survivors at 5 years (1867 ±624 mlmin-1 vs 1259 ±497 mlmin-1, p<0.01). On multivariate Cox regression analysis, the peak VO2 at baseline was the only significant predictor of survival (Table 1b). Conclusion Peak VO2 at baseline was associated with baseline symptom status, the short-term LVEF response to CA and long-term survival and may be a useful stratification tool to aid patient selection for CA.1a. Regression for 6-month LVEF response1b. Regression for long-term mortality

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): NIHR Background Ablation of long-standing persistent atrial fibrillation (LSPAF) is not always successful. The arrhythmia burden was reduced by 75% by 12 months in majority (72%) of patients with LSPAF who underwent surgical or percutaneous ablation in the CASA-AF trial. We hypothesised that biomarker(s) improve prediction of clinical success and offer insights into mechanisms. Objective To identify biomarkers that predict success (75% arrhythmia burden reduction) after ablation for LSPAF at 12-months. Methods Amongst patients participating in the CASA-AF RCT (ISRCTN18250790), pre-ablation serum samples were selected for 20 patients who met criteria for ablation-success at 12 months, and 20 who did not. Olink ProteomicsTM (Sweden) provided analyses using three biomarker panels [inflammation (INFL), cardiovascular III (CVD III), and cell cytology (CELL)] each containing 92 biomarkers. Univariate and multivariable analyses were adjusted for age, sex, BMI, LA diameter and CRP. ROC analysis was undertaken to assess the diagnostic accuracy of the biomarkers. To counter the false discovery rate, Benjamini-Hochberg correction was utilised. Results When patients with ablation-success and -failure were compared, no differences in demographics or cardiac function were found. On univariate analysis, several biomarkers in each panel were associated with ablation-success. Multivariable analysis narrowed the range of biomarkers and identified those that were jointly predictive of outcome: INFL (MCP1 + CD8A + CD40, Figure 1), CVD III (FAS + CPB1) and CELL (GCG + ENTPD6 + IL17RB). These joint biomarkers were analysed using ROC (Figure 2), which showed that increases of biomarkers on the INFL panel (MCP1 + CD8A + CD40) were associated with a greater risk of failure and achieved the highest AUC for prediction of outcome [0.82 (0.75-0.87)]. Conclusion The increase in the serum concentration of markers of inflammation (MCP1 + CD8A + CD40) might be used to identify patients less likely to have sustained benefit from LSPAF ablation. Further studies are required to confirm their prognostic value as pre-procedural biomarkers.

Abstract Funding Acknowledgements Type of funding sources: None. Background Left bundle pacing (LBP) is an evolving pacing method designed to capture the intrinsic conduction and minimise ventricular dys- synchrony. Anatomical complexity, scars of previous corrective surgeries and haemodynamic properties of adult congenital heart disease (ACHD) population could increase challenges of LBP. We describe our experience in LBP in ACHD patients and different patient groups. Purpose To compare the feasibility of LBP in ACHD patient population and non-ACHD patients. Methods We included all patients who had LBP at our institution in 2020 and 2021. Demographic data, imaging data, procedural parameters and follow up data were collected and analysed. Results A total of 36 patients were included and divided into two groups: ACHD (n=8, mean age, 54 years, 38% females) and non-ACHD (n=28, mean age, 74 years, 43% females). ACHD anatomy included simple lesions (4) as atrial and ventricular septal defects, partial anomalous pulmonary venous drainage, bicuspid aortic valve and Shone’s syndrome, moderate (3), as Tetralogy of Fallot with surgical repair, and complex (1), as transposition of great arteries with Mustard repair. Non-ACHD included patients with structurally normal heart, dilated cardiomyopathy, and those who underwent mitral and aortic valve interventions. Mean left ventricular ejection fraction in ACHD group was 59.5%, and 57.5% in non-ACHD. Late gadolinium enhancement in basal septal area was present in 5 patients in ACHD group. Acute success rate, defined as capture of left bundle branch, was 100% in ACHD group, and 88% in non-ACHD. No acute complications were recorded in both groups. Mean pre-procedural QRS duration was longer in ACHD group (170 ms, vs, 120, p=<0.001). Mean reduction in QRS duration in ACHD group was 27 ms, vs, 15, p= 0.856. Mean procedural and fluoroscopy times were similar in both groups (ACHD, 75.5 minutes, vs, 70, p= 0.26, and ACHD, 9 minutes, vs 7.13, respectively, p= 0.46). Pacing parameters at implantation and after 2 months were satisfactory in both groups (Fig 1). Conclusion Left bundle pacing is feasible in ACHD population as compared to non-ACHD patients, with low incidence of complications. Procedural and fluoroscopic times were similar in both groups. Pacing parameters were satisfactory and stable over 2 month-follow up.

Abstract Background Ablation strategy targeting the core of atrial fibrillation (AF) rotors alone can lead to both stabilisation and destabilisation of rotational activity. Non-contact dipole density mapping system is designed to rapidly identify dynamic regional atrial activation patterns of interest (API) during AF. Purpose To assess the feasibility of an ablation strategy consisted of pulmonary vein isolation + targeting the core of APIs followed by linear ablation to the nearest non-conducting boundary to treat persistent AF. Methods The ablation strategy includes: 1. Antral pulmonary vein electrical isolation (APVI); 2. APIs (focal, localised rotational and localised irregular activation; Figure1) detection by dipole density mapping; 3. API core ablation followed by linear ablation to the nearest non-conduction barrier (APVI/mitral valve); 4. repeat step 2 and 3 in LA (RA, if necessary) until sinus rhythm is achieved. Results Consecutive 40 persistent AF patients (mean 62±12 years, 29 males, AF duration 10±4 months, LA diameter 42±9 mm) were included from 2 centres. An average of 2.0±0.7 APIs per patient were targeted post-APVI. Acute AF termination by ablation was achieved in 27/40 (68%) patients. The mean ablation time of APVI and “Core to block” was 33±12 mins and 31±22 mins, respectively. No major complication occurred. During a mean follow-up of 12±5 months, 32/40 patients (80%) maintained sinus rhythm. Conclusion APVI + “Core to block” guided by the dipole density mapping is feasible for treating persistent AF. A larger randomised study is needed to test the effectiveness of this ablation strategy. Acknowledgement/Funding None

Abstract Background Catheter ablation for drug refractory, symptomatic atrial fibrillation (AF), is becoming increasingly common and can be beneficial in alleviating symptoms. However, in the elderly, there are concerns about the risks an invasive procedure poses, with limited published data available in those aged over 80 years. Purpose To determine the complication risk of AF catheter ablation in the elderly Methods Complications were identified from patient records in 3156 consecutive patients who underwent radiofrequency catheter ablation for AF, at a tertiary cardiology centre between 2013–2017. All cases were performed under general anesthesia. Results In this cohort of 3156 patients (mean age= 62.9±11.0 years, female = 29.9%), 90 (2.85%) (mean age= 66±10.0 years, female = 49.5%) complications were identified. In patients aged ≥80 years, complications occurred in 5 out of 99 patients (5.05%) (mean age= 82.6±1.2, female=100%), compared to 85 out of 3057 patients (2.78%) in those aged <80 years (mean age= 65±10.3, female = 49.4%). The difference was not significant p=0.18. Complications in the elderly all occurred acutely, and included groin haematoma (2.02%), pneumonia (2.02%) and pericardial effusion (1.01%). Conclusion Catheter ablation for AF in patients ≥80 years of age, is not associated with a significant increase in complication risk, compared to those who are younger.

Background: Radiofrequency ablation (RFA) is the cornerstone of atrial fibrillation (AF) management.Electroanatomical remodeling (EAR) is thought to occur with increasing AF burden reducing success rates.Long-standing persistent atrial fibrillation (LSPAF) is the most challenging to treat and the anatomical effect of RFA on the atria and ventricles has yet to be understood.Objective: To evaluate the effect of left atrial (LA) ablation on reverse remodeling (RRM) and its outcomes in LSPAF.Methods: Ninety-five patients (64 ± 10 years, 68 males) underwent either thoracoscopic surgical ablation (TSA) or catheter ablation (CA) for LSPAF.Atrio-ventricular volumes and EFs measured at baseline and 6 months' post-ablation using CMR.LA RRM post ablation was defined as a ≥15% reduction in LA maximum volume on 6 months (6M) follow-up MRI.Follow-up also included clinical success defined by sinus rhythm (SR) or AF burden reduction >95% during follow up of mean 295 days. Results:The atrioventricular volumes reduced for all subjects from baseline to 6M following ablation.LA RRM occurred in 61% (58/95) of patients.LA max volume at baseline; [OR 1.06 (1.02 -1.11); p < 0.01] and CA ); p ≤ 0.02] were the only independent predictors of LA RRM in multivariable analysis.Clinical success of ablation after mean 295 ± 70 days was seen in 86% (32/37) vs 64% (37/58) of patients with nonRRM vs RRM respectively (p < 0.02).Improvement of LA EF [OR 1.06 (1.01 -1.11); p < 0.02] post ablation and receiving TSA ); p < 0.05] were independent predictors in multivariate analysis to the maintenance of SR during follow-up.TSA had a higher clinical success rate as opposed to CA; 83.7% vs 61.8%; p < 0.03. Conclusion:This is the first study of LSPAF ablation using two treatment modalities showing LA RRM.Change in LA EF and TSA were independent predictors for successful outcomes.LA RRM occurs with larger atria and hence have a complex LA substrate resulting in less clinical success.Larger studies are required to evaluate this further.

Abstract Background Global simultaneous recording of activation during atrial fibrillation (AF) can elucidate underlying mechanisms contributing to AF maintenance. A better understanding of these mechanisms may allow for a personalised ablation strategy to treat persistent AF. Purpose To characterise left atrial endocardial activation patterns during AF using a novel non-contact dipole density mapping. Methods Activation patterns were characterised into three sub-types: (i) focal with centrifugal activation (FCA); (ii) localised rotational activation (LRA); (iii) localised irregular activation (LIA). Continuous activation patterns were quantified and distributed in the left atrium. Results A total of 144 persistent AF segments with 1068 activation patterns from 25 patients were analysed. The most common pattern was LIA (63%), which consist of four disparate features: slow conduction (45%), pivoting (30%), collision (16%) and acceleration (7%). LRA was the second commonest pattern (20%). FCA (17%) arose frequently from the PVs/ostia. Continuous AF activations comprise multiple combinations of FCA, LRA and LIA, transitioning from one to the next without a discernible order. Preferential conduction areas were typically seen in mid-anterior (48%) and lower-posterior (40%) walls where dominant activations were made up of LRA and LIA. Conclusion AF is characterised by heterogenous activation patterns that vary between individuals. Clinical implications of individualised ablation strategies guided by dipole density mapping will have to be determined. Acknowledgement/Funding None

Abstract Background The association of atrial fibrillation (AF) with thromboembolic stroke due to stasis in the left atrium and left atrial appendage is well described. Whether AF is associated with a systemic prothrombotic state, detectable in peripheral blood, unclear. Previous studies have been inconsistent, with some very small previous studies (<30 patients each) variably indicating that patients with AF may have raised platelet reactivity and levels of antithrombin III, d-dimer, PAI-1 and t-PA-PAI complexes. These cumbersome laboratory tests of coagulation and fibrinolysis are not readily available in the clinical setting. Purpose It was our aim to compare, in peripheral venous blood, thrombotic and endogenous fibrinolytic profile of healthy volunteers and patients with newly diagnosed nonvalvular atrial fibrillation (NVAF), using a point-of-care technique. Methods In a prospective observational study, venous blood samples were taken from 98 healthy volunteers and 100 patients with newly diagnosed NVAF in the out-patient setting. Patients with newly diagnosed NVAF had venous blood tested before any treatment was initiated with aspirin or oral anticoagulation. Thrombotic status was assessed using the Global Thrombosis Test (GTT), a point-of-care test using native non-coagulated blood, assessed within 15 sec of blood withdrawal. The time to form an occlusive venous thrombus in native (non-citrated) blood, a measure of platelet reactivity (occlusion time, OT) and the time taken to spontaneous endogenous fibrinolysis to restore flow (lysis time, LT) were assessed. Results Basic blood tests (full blood count, renal and liver function, inflammatory markers) were normal in all subjects. The groups were matched for sex and race. Mean age of the healthy cohort was 34±8 years and patients 65±10 years. Endogenous fibrinolysis was markedly impaired in patients with NVAF compared to healthy individuals as shown by markedly prolonged LT (median 2015s [interquartile range IQR 1555–2507] vs. 1124s [IQR 919–1554], p<0.ehz745.11201). There was no difference in platelet reactivity between patients and normal volunteers (369s [IQR 308–445]vs 368s [IQR 309–441], p=0.704). Sensitivity analysis was performed on a subgroup matched for age, sex and race. LT remained significantly longer in patients with NVAF compared to controls (1569s [IQR 1499–2244] vs. 1219s [IQR 943–1560], p=0.03), with no difference in platelet reactivity (p=NS). Conclusion In the largest study to date and using a clinically-friendly automated point-of-care technique, we show that patients with NVAF exhibit a systemic prothrombotic state, attributable to significantly impaired endogenous fibrinolysis compared with healthy volunteers. Further studies are needed to see if this could become a screening test for the prothrombotic state in patients with NVAF. Acknowledgement/Funding None

added if cardioversion was needed.The breathing stop more than 30 seconds was defined as apnea.Results: Mean age was 63.9 years and 90 were men.Mean follow-up duration was 2.8 years.Mean CHA2DS2-VASc score was 2.2 and mean body mass index(BMI) was 23.8.16 patients revealed apnea during performing catheter ablation, and their BMI was clearly higher than that of patients without apnea(mean BMI: 26.2 vs. 23.5, p¼0.001).Moreover, their minimum saturation of arterial blood oxygen(SpO2) was significantly lower than that of patients without apnea(mean SpO2 : 89.0% vs. 95.0%,P<0.001).On the other hand, an operative time was not different between patients with apnea and without apnea (206.8 min vs. 204.8min, p¼0.85).36 patients had recurrence of AF and/or atrial tachycardia(AT) after 90 days from PVI, and there was not significant difference of probability of recurrence between patients with apnea and without apnea.And patients with apnea did not have any complication, but 1 pericardial tamponade, 2 gastric hypomotility, and 1 acute coronary syndrome were recognized in patients without apnea.4 patients of all with apnea had a diagnosis of SAS after catheter ablation and then they received appropriate therapy.Conclusion: Drug-induced transient apnea and the deep breathing after apnea did not make an operative time longer, brought less complications, and did not affect probability of recurrence of AF and/or AT.It was thought that an operator performed RFCA more carefully when a patient showed apnea and the deep breathing after apnea.

Cardiac arrhythmias are thought to affect over 2 million people per annum in the UK.Symptoms include palpitations, fatigue and breathlessness in addition to anxiety/worry.These symptoms can have a negative impact on a patient's quality of life.Treatment for cardiac arrhythmias includes ablation of cardiac tissue in an effort to reduce or abolish these symptoms.The importance of the patient's perspective is becoming increasingly recognised.Patient Reported Outcome Measures (PROMs) tools are beginning to be used more widely in order to capture the patient's perspective on the success or lack of success of a given procedure.We collected data from people who underwent cardiac ablation for arrhythmia at 3 centres using PROMs tools comprising EQ-5D-5L, with visual analogue scores (VAS),and the Cardiff Cardiac Ablation PROM (C-CAP) which includes symptom severity scores and impact on life scores.Valid questionnaires were completed pre-ablation, post-ablation and at 1 year follow-up.Questionnaire responses at each of the three time-points were compared.In addition outcomes were analysed for different arrhythmia substrates, including: AF, AVNRT, accessory pathways, atrial flutters, ectopic beats and ventricular tachycardia.Data were not normally distributed and thus analysed using the non-parametric Friedman test.Results were visualised through the use of boxplots.A total of 370 patients completed and returned questionnaires for pre-ablation, post-ablation and at 1 year follow-up and so were included for analysis.EQ-5D-5L indices at post-ablation and at 1 year follow-up were significantly higher ( p , 0.001, n ¼ 370) than pre-ablation.VAS scores were also significantly higher ( p , 0.001, n ¼ 363) at post-ablation and 1 year follow-up than pre-ablation.Symptom severity scores were significantly lower ( p , 0.001, n ¼ 275) at postablation and 1 year follow-up than pre-ablation.Impact on life scores were significantly lower ( p , 0.001, n ¼ 319) at post-ablation and 1 year follow-up than pre-ablation.In addition, impact on life scores were significantly lower (p , 0.001) at 1 year follow-up than post-ablation.Results were analysed at substrate level where significant increases in EQ-5D-5L and VAS scores were observed following ablation in addition to significant reductions in impact on life scores and symptom severity.Studies often report the results of successful cardiac ablation without considering or presenting the patient's perspective on the procedure.Conditions suffered by a patient can have a negative impact on their quality of life.PROMs tools help to capture the patient's perspective and allow the success of a procedure to be measured within the context of an individual.Cardiac ablation has been shown to positively impact on a patient's symptoms and their quality of life.Furthermore, cardiac ablation was shown to positively impact on symptoms suffered by patients with different types of arrhythmias.

Cardiac resynchronisation therapy (CRT) is an effective intervention for appropriately selected patients with heart failure, but exactly how it works is uncertain. Recent data suggest that much, or perhaps most, of the benefits of CRT are not delivered by re-coordinating left ventricular dyssynchrony. Atrio-ventricular resynchronization, reduction in mitral regurgitation and prevention of bradycardia are other potential mechanisms of benefit that will vary from one patient to the next and over time. Because there is no single therapeutic target, it is unlikely that any single measure will accurately predict benefit. The only clinical characteristic that appears to be a useful predictor of the benefits of CRT is a QRS duration of >140 ms. Many new approaches are being developed to try to improve the effectiveness of and extend the indications for CRT. These include smart pacing algorithms, better pacing-site targeting, new sensors, multipoint pacing, remote device monitoring and leadless endocardial pacing. Whether CRT is effective in patients with atrial fibrillation or whether adding a defibrillator function to CRT improves prognosis awaits further evidence.

OBJECTIVES:This study sought to assess the clinical efficacy, safety, and clinical utility of a novel electroanatomical mapping system.BACKGROUND:A new mapping system capable of rapidly acquiring detailed maps based on automatic annotation of thousands of points was recently released for clinical use. This is the first description of its utility in humans.METHODS:The first consecutive 20 cases (7 atrial tachycardia, 8 atrial fibrillation, 3 ventricular tachycardia, and 2 ventricular ectopic beat ablations) were analyzed. The system uses a bidirectional deflectable basket catheter with 64 closely spaced mini-electrodes. It automatically accepts and annotates electrograms when a number of predefined criteria are met.RESULTS:Thirty right atrial maps were acquired in 11 (4 to 15) min, consisting of 7,220 (3,467 to 10,947) points, 22 left atrial maps in 11 (6 to 19) min, consisting of 7,818 (4,379 to 12,262) points and 10 left ventricular maps in 37 (14 to 43) min, consisting of 8,709 (2,605 to 15,514) points. The mini-basket catheter could reach all areas of interest without deflectable sheaths. No embolic events, bleeding complications, or endocardial structure damage were observed. Correction of the automatic annotation was performed in 0.02% of points in 4 of 62 maps. The system revealed re-entry circuits of atrial tachyarrhythmias, identified gaps on linear lesions, and identified and correctly annotated the clinical ventricular ectopic beats and channels of slow conduction within ventricular scar.CONCLUSIONS:The novel automatic mapping system was rapid, safe, and efficacious in mapping a variety of cardiac arrhythmias in humans. Further clinical research is needed to optimize its use in the ablation of complex arrhythmias.

Background— Left atrial appendage (LAA) electric isolation is reported to improve persistent atrial fibrillation (AF) ablation outcomes. However, loss of LAA mechanical function may increase thromboembolic risk. Concomitant LAA electric isolation and occlusion as part of conventional AF ablation has never been tested in humans. We therefore evaluated the feasibility, safety, and efficacy of LAA electric isolation and occlusion in patients undergoing long-standing persistent AF ablation. Methods and Results— Patients with long-standing persistent AF (age, 68±7 years; left atrium diameter, 46±3 mm; and AF duration, 25±15 months) underwent AF ablation, LAA electric isolation, and occlusion. Outcomes were compared with a balanced (1:2 ratio) control group who had AF ablation alone. Among 22 patients who underwent ablation, LAA electric isolation was possible in 20. Intraprocedural LAA reconnection occurred in 17 of 20 (85%) patients, predominantly at anterior and superior locations. All were reisolated. LAA occlusion was successful in all 20 patients. There were no major periprocedural complications. Imaging at 45 days and 9 months confirmed satisfactory device position and excluded pericardial effusion. One of twenty (5%) patients had a gap of ≥5 mm requiring anticoagulation. Nineteen of twenty (95%) patients stopped warfarin at 3 months. Without antiarrhythmic drugs, freedom from AF at 12 months after a single procedure was significantly higher in the study group (19/20, 95%) than in the control group (25/40, 63%), P =0.036. Freedom from atrial arrhythmias was demonstrated in 12 of 20 (60%) and 18 of 20 (90%) patients after 1 and ≤2 procedures (mean, 1.3), respectively. Conclusions— Persistent AF ablation, LAA electric isolation, and mechanical occlusion can be performed concomitantly. This technique may improve the success of persistent AF ablation while obviating the need for chronic anticoagulation. Clinical Trial Registration— URL: https://clinicaltrials.gov . Unique identifier: NCT02028130.