Left bundle branch area pacing in congenital heart disease.

AIMS: Left bundle branch area pacing (LBBAP) has been shown to be effective and safe. Limited data are available on LBBAP in the congenital heart disease (CHD) population. This study aims to describe the feasibility and safety of LBBAP in CHD patients compared with non-CHD patients. METHODS AND RESULTS: This is a single-centre, non-randomized observational study recruiting consecutive patients with bradycardia indication. Demographic data, ECGs, imaging, and procedural data including lead parameters were recorded. A total of 39 patients were included: CHD group (n = 13) and non-CHD group (n = 26). Congenital heart disease patients were younger (55 ± 14.5 years vs. 73.2 ± 13.1, P < 0.001). Acute success was achieved in all CHD patients and 96% (25/26) of non-CHD patients. No complications were encountered in either group. The procedural time for CHD patients was comparable (96.4 ± 54 vs. 82.1 ± 37.9 min, P = 0.356). Sheath reshaping was required in 7 of 13 CHD patients but only in 1 of 26 non-CHD patients, reflecting the complex and distorted anatomy of the patients in this group. Lead parameters were similar in both groups; R wave (11 ± 7 mV vs. 11.5 ± 7.5, P = 0.881) and pacing threshold (0.6 ± 0.3 V vs. 0.7 ± 0.3, P = 0.392). Baseline QRS duration was longer in the CHD group (150 ± 28.2 vs. 118.6 ± 26.6 ms, P = 0.002). Despite a numerically greater reduction in QRS and a similar left ventricular activation time (65.9 ± 6.2 vs. 67 ± 16.8 ms, P = 0.840), the QRS remained longer in the CHD group (135.5 ± 22.4 vs. 106.9 ± 24.7 ms, P = 0.005). CONCLUSION: Left bundle branch area pacing is feasible and safe in CHD patients as compared to that in non-CHD patients. Procedural and fluoroscopy times did not differ between both groups. Lead parameters were satisfactory and stable over a short-term follow-up.

Catheter ablation vs. thoracoscopic surgical ablation in long-standing persistent atrial fibrillation: CASA-AF randomized controlled trial.

AIMS: Long-standing persistent atrial fibrillation (LSPAF) is challenging to treat with suboptimal catheter ablation (CA) outcomes. Thoracoscopic surgical ablation (SA) has shown promising efficacy in atrial fibrillation (AF). This multicentre randomized controlled trial tested whether SA was superior to CA as the first interventional strategy in de novo LSPAF. METHODS AND RESULTS: We randomized 120 LSPAF patients to SA or CA. All patients underwent predetermined lesion sets and implantable loop recorder insertion. Primary outcome was single procedure freedom from AF/atrial tachycardia (AT) ≥30 s without anti-arrhythmic drugs at 12 months. Secondary outcomes included clinical success (≥75% reduction in AF/AT burden); procedure-related serious adverse events; changes in patients' symptoms and quality-of-life scores; and cost-effectiveness. At 12 months, freedom from AF/AT was recorded in 26% (14/54) of patients in SA vs. 28% (17/60) in the CA group [OR 1.128, 95% CI (0.46-2.83), P = 0.83]. Reduction in AF/AT burden ≥75% was recorded in 67% (36/54) vs. 77% (46/60) [OR 1.13, 95% CI (0.67-4.08), P = 0.3] in SA and CA groups, respectively. Procedure-related serious adverse events within 30 days of intervention were reported in 15% (8/55) of patients in SA vs. 10% (6/60) in CA, P = 0.46. One death was reported after SA. Improvements in AF symptoms were greater following CA. Over 12 months, SA was more expensive and provided fewer quality-adjusted life-years (QALYs) compared with CA (0.78 vs. 0.85, P = 0.02). CONCLUSION: Single procedure thoracoscopic SA is not superior to CA in treating LSPAF. Catheter ablation provided greater improvements in symptoms and accrued significantly more QALYs during follow-up than SA. CLINICAL TRIAL REGISTRATION: ISRCTN18250790 and ClinicalTrials.gov: NCT02755688.

Characterising the difference in electrophysiological substrate and outcomes between heart failure and non-heart failure patients with persistent atrial fibrillation.

Aims: Characterizing the differences in substrate and clinical outcome between heart failure (HF) and non-heart failure (non-HF) patients undergoing persistent atrial fibrillation (AF) ablation. Methods and results: Using complex fractionated electrograms (CFE) as a surrogate marker of substrate complexity, we compared the bi-atrial substrate in patients with persistent AF with and without HF, at baseline and after ablation, to determine its impact on clinical outcome. In this retrospective analysis of two prospective studies, 60 patients underwent de-novo step-wise left atrial (LA) ablation, 30 with normal left ventricular ejection fraction (LVEF) ≥ 50% (non-HF group) and 30 with LVEF ≤ 35% (HF group). Multiple high-density bi-atrial CFE maps were acquired along with AF cycle length (AFCL) at each procedural stage. Change in bi-atrial CFE areas, AFCL and outcome data were then compared. In the non-HF group, higher CFE-areas were found at baseline and at each step of the procedure in the LA. In both LA and the right atrium (RA), baseline and final CFE area were also higher in the non-HF group. Single procedure, arrhythmia-free survival at 1 year was higher in the HF group compared with the non-HF group (72% vs. 43%, log rank P = 0.04). Final total bi-atrial CFE area was an independent predictor of arrhythmia recurrence. Conclusions: CFE represents an important surrogate marker of atrial substrate complexity. The atrial substrate in persistent AF differs between HF and non-HF with the latter representing a more complex 'primary' bi-atrial myopathy. LA focussed ablation results in more extensive substrate modification in HF and better clinical outcomes as compared with non-HF.

Resource use and clinical outcomes in patients with atrial fibrillation with ablation versus antiarrhythmic drug treatment.

BACKGROUND: The objective of our study was to compare resource use and clinical outcomes among atrial fibrillation (AF) patients who underwent catheter ablation versus antiarrhythmic drug (AAD) treatment. METHODS: A retrospective cohort design using the Clinical Practice Research Data-Hospital Episode Statistics linkage data from England (2008-2013) was used. Patients undergoing catheter ablation treatment for AF were indexed to the date of first procedure. AAD patients with at least two different AAD drugs were indexed to the first fill of the second AAD. Patients were matched using 1:1 propensity matching. Primary endpoints including inpatient and outpatient visits were compared between ablation and AAD cohorts in the 4 months-1 year period after index. Secondary endpoints including heart failure, stroke, cardioversion, mortality, and a composite outcome were compared for the 4 months-3 years post-index period in the two groups. Cox-proportional hazards models were estimated for clinical outcomes comparison. RESULTS: A total of 558 patients were matched in the two groups for resource utilization comparison. The average number of cardiovascular (CV)-related outpatient visits in the 4-12 months post-index period were significantly lower in the ablation group versus the AAD group (1.76 vs 3.57, p < .0001). There was no significant difference in all-cause and CV-related inpatient visits and all-cause outpatient visits among the two groups. For secondary endpoints comparison, 615 matched patients in each group emerged. Ablation patients had 38% lower risk of heart failure (hazard ratio [HR] 0.62, p = 0.0318), 50% lower risk of mortality (HR 0.50, p = 0.0082), and 43% lower risk of experiencing a composite outcome (HR 0.57, p = 0.0009) as compared to AAD treatment cohort. CONCLUSION: AF ablation was associated with significantly lower CV-related outpatient visits, and lower risk of heart failure and mortality versus AAD therapy.

Outcomes and costs of left atrial appendage closure from randomized controlled trial and real-world experience relative to oral anticoagulation.

AIMS: The aim of this study was to analyse randomized controlled study and real-world outcomes of patients with non-valvular atrial fibrillation (NVAF) undergoing left atrial appendage closure (LAAC) with the Watchman device and to compare costs with available antithrombotic therapies. METHODS AND RESULTS: Registry data of LAAC from two centres were prospectively collected from 110 patients with NVAF at risk of stroke, suitable and unsuitable for long-term anticoagulation (age 71.3 ± 9.2 years, CHADS2 2.8 ± 1.2, CHA2DS2-VASc 4.5 ± 1.6, and HAS-BLED 3.8 ± 1.1). Outcomes from PROTECT AF and registry study LAAC were compared with warfarin, dabigatran, rivaroxaban, apixaban, aspirin, and no treatment using a network meta-analysis. Costs were estimated over a 10-year horizon. Uncertainty was assessed using sensitivity analyses. The procedural success rate was 92% (103/112). Follow-up was 24.1 ± 4.6 months, during which annual rates of stroke, major bleeding, and all-cause mortality were 0.9% (2/223 patient-years), 0.9% (2/223 patient-years), and 1.8% (4/223 patient-years), respectively. Anticoagulant therapy was successfully stopped in 91.2% (93/102) of implanted patients by 12 months. Registry study LAAC stroke and major bleeding rates were significantly lower than PROTECT AF results: mean absolute difference of stroke, 0.89% (P = 0.02) and major bleeding, 5.48% (P < 0.001). Left atrial appendage closure achieved cost parity between 4.9 years vs. dabigatran 110 mg and 8.4 years vs. warfarin. At 10 years, LAAC was cost-saving against all therapies (range £1162-£7194). CONCLUSION: Left atrial appendage closure in NVAF in a real-world setting may result in lower stroke and major bleeding rates than reported in LAAC clinical trials. Left atrial appendage closure in both settings achieves cost parity in a relatively short period of time and may offer substantial savings compared with current therapies. Savings are most pronounced among higher risk patients and those unsuitable for anticoagulation.

Relationship between contact force sensing technology and medium-term outcome of atrial fibrillation ablation: a multicenter study of 600 patients.

INTRODUCTION: Contact force sensing (CFS) technology improves acute pulmonary vein isolation durability; however, its impact on the clinical outcome of ablating atrial fibrillation (AF) is unknown. METHODS AND RESULTS: First time AF ablation procedures employing CFS from 4 centers were matched retrospectively to those without CFS in a 1:2 manner by type of AF. Freedom from atrial tachyarrhythmia was defined as the primary outcome measure, and fluoroscopy time the secondary outcome measure. Nineteen possible explanatory variables were tested in addition to CFS. A total of 600 AF ablation procedures (200 using CFS and 400 using non-CFS catheters) performed between 2010 and 2012 (46% paroxysmal, 36% persistent, 18% long-lasting persistent) were analyzed. The mean follow-up duration was 11.4 ± 4.7 months-paroxysmal AF 11.2 ± 4.1 CFS versus 11.3 ± 3.9 non-CFS (P = 0.745)-nonparoxysmal AF 10.4 ± 4.5 CFS versus 11.9 ± 5.4 non-CFS (P = 0.015). The use of a CFS catheter independently predicted clinical success in ablating paroxysmal AF (HR 2.24 [95% CIs 1.29-3.90]; P = 0.004), but not nonparoxysmal AF (HR 0.73 [0.41-1.30]; P = 0.289) in a multivariate analysis that included follow-up duration. Among all cases, the use of CFS catheters was associated with reduced fluoroscopy time in multivariate analysis (reduction by 7.7 [5.0-10.5] minutes; P < 0.001). Complication rates were similar in both groups. CONCLUSIONS: At medium-term follow-up, CFS catheter technology is associated with significantly improved outcome of first time catheter ablation of paroxysmal AF, but not nonparoxysmal AF. Fluoroscopy time was lower when CFS technology was employed in all types of AF ablation procedures.

Organizational index mapping to identify focal sources during persistent atrial fibrillation.

INTRODUCTION: Localized rotors have been implicated in the mechanism of persistent atrial fibrillation (AF). Although regions of highest dominant frequency (DF) on spectral analysis of the left atrium (LA) have been said to identify rotors, other mechanisms such as wavefront collisions will sporadically also generate an inconsistent distribution of high DF. We hypothesized that if drivers of AF were present, their distinctive spectral characteristics would result more from their temporal stability than their high frequency. METHODS AND RESULTS: Ten patients with persistent AF underwent LA noncontact mapping. Following subtraction of far-field ventricular components, noncontact electrograms at 256 sites underwent fast Fourier transform. Mean absolute difference in DF between 5 sequential 7-second segments of AF was defined as the DF variability (DFV) at each site. Mean ratio of the DF and its harmonics to the total power of the spectrum was defined as the organizational index (OI). Mean DFV was significantly lower in organized areas (OI > 1 SD above mean) than at all sites (0.34 ± 0.04 vs 0.46 ± 0.04 Hz; P < 0.001). When organized areas were ablated during wide-area circumferential ablation, AF organized in remote regions (LA appendage ΔOI ablated vs unablated: +0.21 [0.06-0.41] vs -0.04 [-0.14-0.05]; P = 0.005). CONCLUSIONS: At sites of organized activation, the activation frequency was also significantly more stable over time. This observation is consistent with the existence of focal sources, and inconsistent with a purely random activation pattern. Ablation of such regions is technically feasible, and was associated with organization of AF in remote atrial regions.

Remote monitoring of atrial fibrillation recurrence using mHealth technology (REMOTE-AF).

Aims: This proof-of-concept study sought to evaluate changes in heart rate (HR) obtained from a consumer wearable device and compare against implantable loop recorder (ILR)-detected recurrence of atrial fibrillation (AF) and atrial tachycardia (AT) after AF ablation. Methods and results: REMOTE-AF (NCT05037136) was a prospectively designed sub-study of the CASA-AF randomized controlled trial (NCT04280042). Participants without a permanent pacemaker had an ILR implanted at their index ablation procedure for longstanding persistent AF. Heart rate and step count were continuously monitored using photoplethysmography (PPG) from a commercially available wrist-worn wearable. Photoplethysmography-recorded HR data were pre-processed with noise filtration and episodes at 1-min interval over 30 min of HR elevations (Z-score = 2) were compared with corresponding ILR data. Thirty-five patients were enrolled, with mean age 70.3 ± 6.8 years and median follow-up 10 months (interquartile range 8-12 months). Implantable loop recorder analysis revealed 17 out of 35 patients (49%) had recurrence of AF/AT. Compared with ILR recurrence, wearable-derived elevations in HR ≥ 110 beats per minute had a sensitivity of 95.3%, specificity 54.1%, positive predictive value (PPV) 15.8%, negative predictive value (NPV) 99.2%, and overall accuracy 57.4%. With PPG-recorded HR elevation spikes (non-exercise related), the sensitivity was 87.5%, specificity 62.2%, PPV 39.2%, NPV 92.3%, and overall accuracy 64.0% in the entire patient cohort. In the AF/AT recurrence only group, sensitivity was 87.6%, specificity 68.3%, PPV 53.6%, NPV 93.0%, and overall accuracy 75.0%. Conclusion: Consumer wearable devices have the potential to contribute to arrhythmia detection after AF ablation. Study Registration: ClinicalTrials.gov Identifier: NCT05037136 https://clinicaltrials.gov/ct2/show/NCT05037136.

Sex Differences in the Clinical Presentation and Natural History of Dilated Cardiomyopathy.

BACKGROUND: Biological sex has a diverse impact on the cardiovascular system. Its influence on dilated cardiomyopathy (DCM) remains unresolved. OBJECTIVES: This study aims to investigate sex-specific differences in DCM presentation, natural history, and prognostic factors. METHODS: The authors conducted a prospective observational cohort study of DCM patients assessing baseline characteristics, cardiac magnetic resonance imaging, biomarkers, and genotype. The composite outcome was cardiovascular mortality or major heart failure (HF) events. RESULTS: Overall, 206 females and 398 males with DCM were followed for a median of 3.9 years. At baseline, female patients had higher left ventricular ejection fraction, smaller left ventricular volumes, less prevalent mid-wall myocardial fibrosis (23% vs 42%), and lower high-sensitivity cardiac troponin I than males (all P < 0.05) with no difference in time from diagnosis, age at enrollment, N-terminal pro-B-type natriuretic peptide levels, pathogenic DCM genetic variants, myocardial fibrosis extent, or medications used for HF. Despite a more favorable profile, the risk of the primary outcome at 2 years was higher in females than males (8.6% vs 4.4%, adjusted HR: 3.14; 95% CI: 1.55-6.35; P = 0.001). Between 2 and 5 years, the effect of sex as a prognostic modifier attenuated. Age, mid-wall myocardial fibrosis, left ventricular ejection fraction, left atrial volume, N-terminal pro-B-type natriuretic peptide, high-sensitivity cardiac troponin I, left bundle branch block, and NYHA functional class were not sex-specific prognostic factors. CONCLUSIONS: The authors identified a novel paradox in prognosis for females with DCM. Female DCM patients have a paradoxical early increase in major HF events despite less prevalent myocardial fibrosis and a milder phenotype at presentation. Future studies should interrogate the mechanistic basis for these sex differences.

Long-term clinical outcomes and cost-effectiveness of catheter vs thoracoscopic surgical ablation in long-standing persistent atrial fibrillation using continuous cardiac monitoring: CASA-AF randomized controlled trial.

BACKGROUND: Long-term clinical outcomes of catheter ablation (CA) compared to thoracoscopic surgical ablation (SA) to treat patients with long-standing persistent atrial fibrillation (LSPAF) are not known. OBJECTIVE: The purpose of this study was to compare the long-term (36-month) clinical efficacy, quality of life, and cost-effectiveness of SA and CA in LSPAF. METHODS: Participants were followed up for 3 years using implantable loop recorders and questionnaires to assess the change in quality of life. Intention-to-treat analyses were used to report the findings. RESULTS: Of the 115 patients with LSPAF treated, 104 (90.4%) completed 36-month follow-up [CA: n = 57 (95%); SA: n = 47 (85%)]. After a single procedure without antiarrhythmic drugs, 7 patients (12%) in the CA arm and 5 (11%) in the SA arm [hazard ratio 1.22; 95% confidence interval (CI) 0.81-1.83; P = .41] were free from atrial fibrillation/tachycardia (AF/AT) ≥30 seconds at 36 months. Thirty-three patients (58%) in the CA arm and 26 (55%) in the SA arm (hazard ratio 1.04; 95% CI 0.57-1.88; P = .91) had their AF/AT burden reduced by ≥75%. The overall impact on health-related quality of life was similar, with mean quality-adjusted life year estimates of 2.45 (95% CI 2.31-2.59) for CA and 2.32 (95% CI 2.13-2.52) for SA. Estimated costs were higher for SA (mean £24,682; 95% CI £21,746-£27,618) than for CA (mean £18,002; 95% CI £15,422-£20,581). CONCLUSION: In symptomatic LSPAF, CA and SA were equally effective at achieving arrhythmia outcomes (freedom from AF/AT ≥30 seconds and ≥75% burden reduction) after a single procedure without antiarrhythmic drugs. However, SA is significantly more costly than CA. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT04280042.

United Kingdom national experience of entirely subcutaneous implantable cardioverter-defibrillator technology: important lessons to learn.

AIMS: The aim of this study was to describe the early phase United Kingdom (UK) clinical experience with a novel entirely subcutaneous implantable cardioverter-defibrillator (S-ICD). METHODS AND RESULTS: A questionnaire was sent to all UK hospitals implanting S-ICDs. Nineteen of 25 (76%) hospitals responded with the details of 111 implanted patients [median 5/hospital (range 1-18)]. Mean duration of follow-up was 12.7 ± 7.1 months. Median patient age was 33 years (range 10-87 years). Underlying pathology was primary electrical disease in 43%, congenital heart disease 12%, hypertrophic cardiomyopathy 20%, ischaemic cardiomyopathy 14%, idiopathic dilated cardiomyopathy 5%, and other cardiomyopathies 7% patients. Nineteen (17%) patients required 20 re-operations, including permanent device explantation in 10 (9%). Twenty-four appropriate shocks were delivered in 13 (12%) patients, including 10 for ventricular fibrillation. One patient suffered arrhythmic death, but there were no failures to detect or terminate ventricular arrhythmias above the programmed detection rate. Fifty-one inappropriate shocks were delivered in 17 (15%) patients. Forty-one (80%) were for T-wave over-sensing and 1 (2%) for atrial flutter-wave over-sensing. The 11 patients who received inappropriate shocks due to T-wave over-sensing were significantly younger than patients who did not (24 ± 10 vs. 37 ± 19 years; P = 0.02). CONCLUSION: The S-ICD is an important innovation in ICD technology. However, these data indicate that adverse event rates are significant during early clinical adoption. Important lessons in patient selection, implant technique, and device programming can be learnt from this experience.

Clinical experience of entirely subcutaneous implantable cardioverter-defibrillators in children and adults: cause for caution.

AIMS: This paper describes our clinical experience of using an entirely subcutaneous implantable cardioverter-defibrillator (S-ICD) in children and adults. Maintaining lead integrity and long-term vascular access are critical challenges of ICD therapy, especially in younger patients. The S-ICD has considerable theoretical advantages in selected patients without pacing indications, particularly children and young adults. Although sensing in an S-ICD may be influenced by age, pathology, and posture, there are currently few published data on clinical sensing performance outside the setting of intra-operative testing or in younger patients. METHODS AND RESULTS: Patients were selected by a multi-disciplinary team on clinical grounds for S-ICD implantation from a broad population at risk of sudden arrhythmic death. Sixteen patients underwent implantation [median age 20 years (range 10-48 years)]. Twelve had primary electrical disease and four had congenital structural heart disease. There were no operative complications, and ventricular fibrillation (VF) induction testing was successful in all cases. During median follow-up of 9 months (range 3-15 months), three children required re-operation. Eighteen clinical shocks were delivered in six patients. Ten shocks in four patients were inappropriate due to T-wave over-sensing. Within the eight shocks for ventricular arrhythmia, three were delivered for VF, among which two had delays in detection with time to therapy of 24 and 27 s. CONCLUSION: The S-ICD is an important new option for some patients. However, these data give cause for caution in light of the limited published data regarding clinical sensing capabilities, particularly among younger patients.

Conduction system pacing learning curve: Left bundle pacing compared to His bundle pacing.

Introduction: Conduction system pacing (CSP), consisting of His bundle pacing (HBP) or left bundle branch area pacing (LBBAP) is a rapidly developing field. These pacing techniques result in single lead left ventricular resynchronisation. Understanding of the associated learning curve of the two techniques is an important consideration for new implanters/implanting centres. Methods: We conducted a review of the first 30 cases of both HBP and LBBAP at The Royal Brompton Hospital. The procedural duration and fluoroscopy time were used as surrogates for the learning curve of each technique. Results: Patient characteristics were similar in HBP and LBBAP groups; LV ejection fraction (46% vs 54%, p = 0.08), pre-procedural QRS duration (119 ms vs 128 ms, p = 0.32).Mean procedural duration was shorter for LBBAP than for HBP (87 vs 107mins, p = 0.04) and the drop in procedural duration was more marked in LBBAP, plateauing and remaining low at 80mins after the initial 10 cases. Fluoroscopic screening time mirrored procedural duration (8 min vs 16 min, p < 0.01). Discussion/Conclusion: Our data suggest that the CSP learning curve was shorter for LBBAP than for HBP and appears to plateaux after the first 10 cases, however the HBP learning curve is longer with continued improvement over the first 30 cases. The shorter learning curve of LBBAP in conjunction with the superior electrical parameters and simplified programming mean the establishment of a CSP program is potentially easier with LBBAP compared to with HBP.

Left Atrial Function Predicts Atrial Arrhythmia Recurrence Following Ablation of Long-Standing Persistent Atrial Fibrillation.

BACKGROUND: Left atrial (LA) function following catheter or surgical ablation of de-novo long-standing persistent atrial fibrillation (AF) and its impact on AF recurrence was studied in patients participating in the CASA-AF trial (Catheter Ablation vs. Thoracoscopic Surgical Ablation in Long Standing Persistent Atrial Fibrillation). METHODS: All patients underwent echocardiography preablation, 3 and 12 months post-ablation. LA structure and function were assessed by 2-dimensional volume and speckle tracking strain measurements of LA reservoir, conduit, and contractile strain. Left ventricular diastolic function was measured using transmitral Doppler filling velocities and myocardial tissue Doppler velocities to derive the e', E/e', and E/A ratios. Continuous rhythm monitoring was achieved using an implantable loop recorder. RESULTS: Eighty-three patients had echocardiographic data suitable for analysis. Their mean age was 63.6±9.7 years, 73.5% were male, had AF for 22.8±11.6 months, and had a mean LA maximum volume of 48.8±13.8 mL/m2. Thirty patients maintained sinus rhythm, and 53 developed AF recurrence. Ablation led to similar reductions in LA volumes at follow-up in both rhythm groups. However, higher LA emptying fraction (36.3±10.6% versus 27.9±9.9%; P<0.001), reservoir strain (22.6±8.5% versus 16.7±5.7%; P=0.001), and contractile strain (9.2±3.4% versus 5.6±2.5%; P<0.001) were noted in the sinus rhythm compared with AF recurrence group following ablation at 3 months. Diastolic function was better in the sinus rhythm compared with the AF recurrence group with an E/A ratio of 1.5±0.5 versus 2.2±1.2 (P<0.001) and left ventricular E/e' ratio of 8.0±2.1 versus 10.3±4.1 (P<0.001), respectively. LA contractile strain at 3 months was the only independent predictor of AF recurrence. CONCLUSIONS: Following ablation for long-standing persistent AF, improvement in LA function was greater in those who maintained sinus rhythm. LA contractile strain at 3 months was the most important determinant of AF recurrence following ablation. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02755688.

Beyond pulmonary vein isolation for persistent atrial fibrillation: sequential high-resolution mapping to guide ablation.

PURPOSE: We aimed to evaluate whether outcomes with ablation in persistent (PsAF) and long-standing persistent (LsPsAF) AF can be improved beyond what can be achieved with pulmonary vein isolation (PVI) alone, using individualized mapping to guide ablation. METHODS: We studied 20 pts (15 M, 68 ± 11y) with PsAF (14) or LsPsAF (6) referred for first-time AF ablation. Following antral PVI, individualized mapping (IM) was performed using a high-density mapping catheter stably and fully deployed for 30 s at each of 23 ± 9 sites per patient. Activation data were reviewed, and an ablation strategy designed to intersect areas of focal and rotational activity. Mean follow-up was 429 ± 131 days. The study population was compared to a matched contemporary control cohort (CC) of 20 consecutive patients undergoing conventional ablation. RESULTS: Despite the IM group having a higher median comorbidities score, 3.5 vs. 2.5 in the CC group, indicating potentially more complex patients and more advanced substrate, cumulative freedom from AF after a single procedure was achieved in 94% of patients in the IM group vs. 75% in the CC group at 1 year and remained the same in both groups at the conclusion of the study (p = 0.02). There was a similar trend in atrial arrhythmia-free survival between both groups (84% vs. 67% at 1 year) that did not reach statistical significance. The procedure duration was longer in the IM group by a median of 31.5 min (p = 0.004). CONCLUSIONS: Individualized mapping to guide AF ablation appears to achieve significantly greater AF-free survival compared to conventional PVI when applied as a primary ablation treatment. The results of this pilot study need to be confirmed in a larger, randomized trial.

Moderate excess alcohol consumption and adverse cardiac remodelling in dilated cardiomyopathy.

OBJECTIVE: The effect of moderate excess alcohol consumption is widely debated and has not been well defined in dilated cardiomyopathy (DCM). There is need for a greater evidence base to help advise patients. We sought to evaluate the effect of moderate excess alcohol consumption on cardiovascular structure, function and outcomes in DCM. METHODS: Prospective longitudinal observational cohort study. Patients with DCM (n=604) were evaluated for a history of moderate excess alcohol consumption (UK government guidelines; >14 units/week for women, >21 units/week for men) at cohort enrolment, had cardiovascular magnetic resonance and were followed up for the composite endpoint of cardiovascular death, heart failure and arrhythmic events. Patients meeting criteria for alcoholic cardiomyopathy were not recruited. RESULTS: DCM patients with a history of moderate excess alcohol consumption (n=98, 16%) had lower biventricular function and increased chamber dilatation of the left ventricle, right ventricle and left atrium, as well as increased left ventricular hypertrophy compared with patients without moderate alcohol consumption. They were more likely to be male (alcohol excess group: n=92, 94% vs n=306, 61%, p=<0.001). After adjustment for biological sex, moderate excess alcohol was not associated with adverse cardiac structure. There was no difference in midwall myocardial fibrosis between groups. Prior moderate excess alcohol consumption did not affect prognosis (HR 1.29, 95% CI 0.73 to 2.26, p=0.38) during median follow-up of 3.9 years. CONCLUSION: DCM patients with moderate excess alcohol consumption have adverse cardiac structure and function at presentation, but this is largely due to biological sex. Alcohol may contribute to sex-specific phenotypic differences in DCM. These findings help to inform lifestyle discussions for patients with DCM.

Precision Phenotyping of Dilated Cardiomyopathy Using Multidimensional Data.

BACKGROUND: Dilated cardiomyopathy (DCM) is a final common manifestation of heterogenous etiologies. Adverse outcomes highlight the need for disease stratification beyond ejection fraction. OBJECTIVES: The purpose of this study was to identify novel, reproducible subphenotypes of DCM using multiparametric data for improved patient stratification. METHODS: Longitudinal, observational UK-derivation (n = 426; median age 54 years; 67% men) and Dutch-validation (n = 239; median age 56 years; 64% men) cohorts of DCM patients (enrolled 2009-2016) with clinical, genetic, cardiovascular magnetic resonance, and proteomic assessments. Machine learning with profile regression identified novel disease subtypes. Penalized multinomial logistic regression was used for validation. Nested Cox models compared novel groupings to conventional risk measures. Primary composite outcome was cardiovascular death, heart failure, or arrhythmia events (median follow-up 4 years). RESULTS: In total, 3 novel DCM subtypes were identified: profibrotic metabolic, mild nonfibrotic, and biventricular impairment. Prognosis differed between subtypes in both the derivation (P < 0.0001) and validation cohorts. The novel profibrotic metabolic subtype had more diabetes, universal myocardial fibrosis, preserved right ventricular function, and elevated creatinine. For clinical application, 5 variables were sufficient for classification (left and right ventricular end-systolic volumes, left atrial volume, myocardial fibrosis, and creatinine). Adding the novel DCM subtype improved the C-statistic from 0.60 to 0.76. Interleukin-4 receptor-alpha was identified as a novel prognostic biomarker in derivation (HR: 3.6; 95% CI: 1.9-6.5; P = 0.00002) and validation cohorts (HR: 1.94; 95% CI: 1.3-2.8; P = 0.00005). CONCLUSIONS: Three reproducible, mechanistically distinct DCM subtypes were identified using widely available clinical and biological data, adding prognostic value to traditional risk models. They may improve patient selection for novel interventions, thereby enabling precision medicine.

Internationally validated score to predict the outcome of non-paroxysmal atrial fibrillation ablation: the 'FLAME score'.

BACKGROUND: The clinical effectiveness of ablating non-paroxysmal atrial fibrillation (non-PAF) relies on proper patient selection. We developed and validated a scoring system to predict non-PAF ablation outcomes. METHODS: Data on 416 non-PAF ablations were analysed using binary logistic regression at a London centre. Identified preprocedural variables, which independently predicted freedom from atrial tachyarrhythmia. Twenty-one possible predictive variables and a model with c-statistic 0.751-explained outcome variation in London at mean follow-up 12±3 months. An additive point score (range 0-9) was developed-the FLAME score: female=1; long-lasting persistent atrial fibrillation=1; left atrial diameter in mm: 40 to <45 = 1, 45 to <50 = 2, 50 to <55=3, ≥55 =4; mitral regurgitation (MR) mild to moderate=1; extreme comorbidity=2. Extreme comorbidities include severe MR, moderate mitral stenosis, mitral replacement, hypertrophic cardiomyopathy or congenital heart disease. RESULTS: The FLAME score was applied to data (882 non-PAF ablations) at a Californian centre, and predicted the outcome of both single (p<0.0001) and multiple (p<0.0001) procedures. For first ablation (follow-up 2.1 years (median, IQR 1.0-4.1)), FLAME score: 0-1 predicts 62% success, 2-4 44% and ≥5 29% (Ptrend <0.0001). After the final ablation (mean procedures: 1.4±0.6, follow-up 1.8 years (median, IQR 0.8-3.6)), FLAME score: 0-1 predicts 81% success, 2-4 65% and ≥5 44% (Ptrend <0.0001). CONCLUSIONS: FLAME score is easily calculated, derived in London, and predicted single and multiple procedural outcomes for non-PAF ablations in California. In patients with a high score, even multiple procedures are usually ineffective.

Catheter Ablation of Atrial Fibrillation in Patients With Functional Mitral Regurgitation and Left Ventricular Systolic Dysfunction.

Background: The efficacy of catheter ablation for atrial fibrillation (AF) in patients with functional mitral regurgitation (MR) and left ventricular (LV) systolic dysfunction (LVSD) is not known. The aim of the study is to determine the efficacy of catheter ablation for AF in patients with functional MR and LVSD, and to validate its effects on the severity of MR and cardiac reverse remodeling. Methods: We performed a retrospective study of 54 patients with functional MR who underwent AF ablation, including 21 (38.9%) with LVSD and 33 (61.1%) with normal LV systolic function (LVF). The primary outcomes evaluated were freedom from recurrent atrial tachyarrhythmia (ATa), severity of MR, and left atrial (LA) and LV remodeling. Results: During a mean follow-up of 20.7 ± 16.8 months, freedom from recurrent ATa was not significantly different between patients with LVSD and those with normal LVF after the first ablation (P = 0.301) and after multiple ablations (P = 0.728). Multivariable predictors of recurrent ATa were AF duration [hazard ratio (HR) 1.12, 95% confidence interval (CI) 1.01-1.25; P = 0.039), previous stroke (HR 5.28, 95% CI 1.46-19.14; P = 0.011), and estimated glomerular filtration rate (HR 0.97, 95% CI 0.95-0.99; P = 0.012). Compared with baseline, there was a significant reduction in severity of MR (P = 0.007), LA size (P < 0.001) and LV end-systolic dimension (P = 0.008), and improvement in the LV ejection fraction (P = 0.001) after restoring sinus rhythm in patients with LVSD. Conclusion: Catheter ablation is a valid option for the treatment of AF in patients with functional MR and LVSD, even though multiple procedures may be required.