History Of AF Research Articles

Abstract 13436: Sex-Specific Predictors of Postoperative Atrial Fibrillation and the Role of Cardiometabolic Diseases

Introduction: Cardiometabolic diseases increase the risk of postoperative atrial fibrillation (POAF), which in turn is associated with higher long-term risk of major cardiovascular events (MACE). Little is known regarding the sex-specific impact of cardiometabolic diseases on POAF risk. We evaluated the sex-specific predictors of POAF after coronary artery bypass grafting (CABG), with a focus on preoperative cardiometabolic profile. Methods: In a prospective registry of patients undergoing isolated CABG (2006-2019), we compared predictors of POAF between sexes. We excluded patients with previous AF history, redo/urgent/off-pump CABG, perioperative mortality, and permanent pacemakers/defibrillators. Abdominal obesity was defined as a waist circumference (WC) >102 cm (men [M]) or >88 cm (women [W]). Results: We included 7,851 patients (19% women). Baseline characteristics are presented in Table 1. POAF occurred in 27% of women and 31% of men (p<0.01). Women were older and had a higher prevalence of comorbidities, abdominal obesity and a worse lipid profile. In a logistic regression model adjusting for the variables in Table 1, men had a higher risk of POAF (OR M = 1.4 [1.2-1.6], p<0.01). When stratifying by sex, significant predictors (p<0.05) of POAF for both sexes were age, WC (OR M = 1.04 [1.00-1.08]; OR W = 1.01 [1.00-1.03]), and triglycerides (TG) (OR M = 0.98 [0.97-0.99]; OR W = 0.97 [0.95-0.99]). Sex-specific predictors were creatinine for women and beta-blockers, extracorporeal circulation time, intensive care stay and hemoglobin for men. Conclusions: Women had less POAF but worse preoperative cardiometabolic profile compared to men. WC was a strong predictor of POAF for both sexes, while higher TG levels were protective. Since POAF is linked to future risk of MACE, the preoperative clinical assessment of WC should be encouraged and targeted for preventive strategies, especially in women. More studies are needed to investigate the role of TG in POAF.

Association of blood-based biomarkers with radiologic markers and cognitive decline in atrial fibrillation patients

BackgroundAtrial fibrillation (AF) has been associated with an increased risk of silent brain infarcts (SBI) and cognitive impairment, even in patients with low embolic risk. We aimed to test the association between 11 blood-biomarkers representing different AF-related pathways, and SBI, white matter hyperintensities (WMH), and cognitive decline in patients with AF and low embolic risk. MethodsThe present study followed a cross-sectional design. 70 patients with a history of AF and CHADS2 score ≤1, and 10 controls with neither AF nor SBI were included. All patients underwent a 3T brain MRI. Cortical and large subcortical ischemic lesions were considered presumed embolic origin lesions. White matter hyperintensities (WMH) were measured according to the Fazekas scale. A subset of patients underwent cognitive evaluation with the MoCA test. Circulating proteins were measured under blind conditions in a laboratory at Roche Diagnostics, Germany. Results45 patients presented SBI in the MRI, and 25 did not. Ang-2, FGF-23, and BMP-10 were increased in patients with SBI. Ang-2 was elevated only in patients with embolic infarcts, whereas FGF-23 and BMP-10 tended to be elevated in patients with both types of infarcts. Ang-2 (OR = 1.56 [0.94-2.59], p = 0.087), and BMP-10 (OR = 4.83 [0.99–23.60], p = 0.052) were the biomarkers that showed the highest association with SBI when entered in a multivariable logistic regression model corrected by age. No biomarker was found associated with WMH or mild cognitive impairment. ConclusionsBMP-10, and Ang-2 were increased in patients with SBI. Its usefulness to detect SBI in AF patients should be further explored.

Comprehensive bioinformatics analysis reveals common potential mechanisms, progression markers, and immune cells of coronary virus disease 2019 and atrial fibrillation

Atrial fibrillation (AF) is the most common arrhythmia in coronary virus disease 2019 (COVID-19) patients, especially in severe patients. A history of AF can exacerbate COVID-19 symptoms. COVID-19 Patients with new-onset AF have prolonged hospital stays and increased death risk. However, the mechanisms and targets of the interaction between COVID-19 and AF have not been elucidated. We used a series of bioinformatics analyses to understand biological pathways, protein-protein interaction (PPI) networks, gene regulatory networks (GRNs), and protein-chemical interactions between COVID-19 and AF and constructed an AF-related gene signature to assess COVID-19 severity and prognosis. We found folate and one-carbon metabolism, calcium regulation, and TFG-β signaling pathway as potential mechanisms linking COVID-19 and AF, which may be involved in alterations in neutrophil metabolism, inflammation, and endothelial cell function. We identified hug genes and found that NF-κb, hsa-miR-1-3p, hsa-miR-124-3p, valproic acid, and quercetin may be key regulatory molecules. We constructed a 3-gene signature consisting of ARG1, GIMAP7, and RFX2 models for the assessment of COVID-19 severity and prognosis, and found that they are associated with neutrophils, T cells, and hematopoietic stem cells, respectively. Our study reveals a dysregulation of metabolism, inflammation, and immunity between COVID-19 and AF, and identified several therapeutic targets and progression markers. We hope that the results will reveal important insights into the complex interactions between COVID-19 and AF that will drive novel drug development and help in severity assessment.

Mortality risk factors in patients with SARS-CoV-2 infection and atrial fibrillation: Data from the SEMI-COVID-19 registry

IntroductionAtrial fibrillation and associated comorbidities pose a risk factor for mortality, morbidity and development of complications in patients admitted for COVID-19. ObjectivesTo describe the clinical, epidemiological, radiological and analytical characteristics of patients with AF admitted for COVID-19 in Spain. Secondarily, we aim to identify those variables associated with mortality and poor prognosis of COVID-19 in patients with AF. MethodsRetrospective, observational, multicenter, nationwide, retrospective study of patients hospitalized for COVID-19 from March 1 to October 1, 2020. Data were obtained from the SEMI-COVID-19 Registry of the Spanish Society of Internal Medicine (SEMI) in which 150 Spanish hospitals participate. ResultsBetween March 1 and October 1, 2020, data from a total of 16,461 patients were entered into the SEMI-COVID-19 registry. 1,816 (11%) had a history of AF and the number of deaths among AF patients amounted to 738 (41%). Regarding clinical characteristics, deceased patients were admitted with a higher heart rate (88.38 vs 84.95; p > 0.01), with a higher percentage of respiratory failure (67.2% vs 20.1%; p < 0.01) and high tachypnea (58% vs 30%; p < 0.01). The comorbidities that presented statistically significant differences in the deceased group were: age, hypertension and diabetes with target organ involvement. There was also a higher prevalence of a history of cardiovascular disease in the deceased. On multivariate analysis, DOACs treatment had a protective role for mortality (OR:0,597) IC (0,402-0,888 ; p = 0.011). ConclusionsPrevious treatment with DOACs and DOACs treatment during admission seem to have a protective role in patients with AF, although this fact should be verified in prospective studies.

The impact of statin on post-operative atrial fibrillation after discharge from cardiac surgery: secondary analysis of the SEARCH-AF CardioLink-1 randomized trial

Abstract Background There is conflicting evidence regarding the use of statins to reduce the risk of post-operative atrial fibrillation (POAF) in patients undergoing cardiac surgery. Purpose We sought to determine the effects of statin use on the burden of new-onset post-discharge POAF in the Post-Surgical Enhanced Monitoring for Cardiac Arrhythmias and Atrial Fibrillation (SEARCH-AF) CardioLink-1 randomized controlled trial. Methods In the SEARCH-AF trial, 336 patients with risk factors for stroke (CHA2DS2-VASc score ≥2) and no history of preoperative AF were randomized to usual care or continuous cardiac rhythm monitoring for 30 days after discharge from cardiac surgery with a wearable, patched-based device. The primary endpoint was the occurrence of cumulative atrial fibrillation/flutter (AF/AFL) lasting for ≥6 minutes detected by continuous monitoring or AF/AFL documented by a 12-lead electrocardiogram within 30 days of randomization. Using time-to-event analysis and Cox regression, we evaluated the association between the risk of post-operative AF in relation to statin use and dosing intensity (low, moderate, high) at the time of discharge. We excluded patients who experienced post-operative AF during hospitalization in this analysis. Results In the overall cohort (n=336), 260 (77.4%) patients were treated with statins at the time of hospital discharge. There were 18 (5.4%) patients who experienced post-operative AF during hospitalization. Patients prescribed with statins were more likely to be male (p=0.018), had lower CHA2DS2-VASc scores (p=0.011), and were more likely to undergo isolated coronary artery bypass grafting (CABG) (p=0.083). Baseline characteristics were otherwise similar between the 2 groups. Patients treated with statins at discharge had a 2-fold lower rate of post-operative AF than those who were not treated with statins in the overall cohort (17.6% vs. 8.2%, Log-Rank p=0.017) and among those who were randomized to continuous cardiac rhythm monitoring (31.6% vs. 16.0%, Log-Rank p=0.027) (Figure). After adjusting for surgery type (CABG vs. valve surgery) and the CHA2DS2-VASc score, statin use at discharge was associated with a lower risk of post-operative AF within 30 days after surgery (hazard ratio 0.48, 95% CI 0.24–0.97). Furthermore, increasing intensity of statin therapy was associated with lower risk of POAF (ptrend=0.0012) (Figure 1) Conclusion Among cardiac surgery patients with risk factors for stroke and no history of pre-operative AF, the use of statins was associated with a reduction in post-operative AF risk within 30 days of discharge. The routine use of high-intensity statin to prevent post-operative AF after cardiac surgery deserves further study. Funding Acknowledgement Type of funding sources: Other. Main funding source(s): Heart and Stroke Foundation of Canada

The long-term clinical course of moderate tricuspid regurgitation

Abstract Background Moderate TR is a frequent condition, worsening mid and long-term survival, particularly in patients &amp;gt;75 years old, and in those suffering from left ventricular systolic dysfunction. As TR is often clinically unsuspected until an advanced stage of congestive heart failure (HF), there is a great need of early diagnosis and long-term appropriate follow-up. However, data focusing on the clinical and echocardiographic course of a cohort of patients with moderate TR is lacking, and the most appropriate type and time of management of these patients is still heavily debated. Purpose To evaluate the evolution and the long-term clinical outcome of a cohort of patients suffering from moderate and moderate to severe TR, regardless of its etiology. Methods Clinical outcome and echocardiographic follow-up were assessed in 212 patients diagnosed with moderate and moderate to severe TR in our centre between January 2014 and December 2019. TR progression at follow-up was defined as TR grade increase to at least severe. The primary endpoint was all-cause death; secondary endpoints were cardiovascular (CV) death and HF hospitalization. Results After a median follow-up of 4.2 years, TR progression occurred in 76 patients (36%): patients with TR progression presented with more history of coronary artery disease (p=0.042), atrial fibrillation (AF, p=0.007) and chronic kidney disease (CKD, p=0.007) and with baseline larger right ventricle end-diastolic diameter (RVEDD, p&amp;lt;0.001) and worse left ventricular ejection fraction (LVEF, p=0.048). After univariate and multivariate analyses, a history of AF (HR 2.3, CI 1.2–4.5, p=0.011) and RVEDD (HR 2.4, CI 1.3–4.4, p=0.003) were independent predictors of TR progression. The primary endpoint occurred in 57 patients (27%) and was significantly more frequent (p=0.015) in the group of patients with TR progression compared to those without TR progression; multivariate analyses showed TR grade progression (HR 4.3, CI 2.1–9.1, p&amp;lt;0.001), CKD (HR 3.2, CI 1.5–7.1, p=0.002) and LVEF (HR 0.9, CI 0.93–0.99, p=0.007) as being independently associated with the primary outcome. Moreover, both CV death (p=0.003) and HF hospitalization (p=0.0139) were significantly more frequent in patients with TR progression. Conclusions Our results showed that moderate TR, by progressing in a relevant proportion of patients over a long-term follow-up, significantly increases the risk of mortality and HF hospitalization. We identified specific risk factors associated with TR progression, which could help to identify patients at risk before an advanced stage of this disease. We believe that this cohort of patients should be appropriately managed and closely followed-up to avoid adverse clinical events related to the natural course of this valvulopathy. Funding Acknowledgement Type of funding sources: None.

Valvular surgery is associated with an increased risk of post-operative atrial fibrillation: secondary analysis of the SEARCH-AF CardioLink-1 randomized trial

Abstract Background Patients undergoing valve surgery have a higher risk of developing post-operative atrial fibrillation (POAF) relative to those undergoing isolated coronary artery bypass grafting (CABG). Whether this risk extends beyond hospital discharge is unknown. Purpose We examined the association between surgery type (isolated CABG vs. valve repair/replacement) on the incidence of post-operative atrial fibrillation (POAF) by conducting a secondary analysis of the Post-Surgical Enhanced Monitoring for Cardiac Arrhythmias and Atrial Fibrillation (SEARCH-AF) CardioLink-1 randomized trial. Methods In the SEARCH-AF trial, 336 patients with risk factors for stroke (CHA2DS2-VASc score ≥2) and no history of preoperative AF were randomized to usual care or continuous cardiac rhythm monitoring for 30 days after discharge from cardiac surgery with a wearable, patched-based device. The primary outcome was occurrence of cumulative atrial fibrillation/flutter (AF/AFL) lasting for ≥6 minutes detected by continuous monitoring or AF/AFL documented by a 12-lead ECG within 30 days of randomization. We compared the risk of POAF between patients who underwent CABG vs. valve repair/replacement. Patients who experienced post-operative AF during hospitalization were excluded from this analysis. Results The overall cohort consisted of 255, 39, and 42 patients who underwent isolated CABG, isolated valve replacement/repair, and CABG + valve repair/replacement, respectively. Baseline characteristics were similar among the groups except for younger age (p=0.0014), higher prevalence of preoperative myocardial infarction (p=0.002) and lower ejection fraction (p=0.025) in the isolated CABG group. Eighteen patients experienced post-operative AF during hospitalization. Patients who underwent CABG + valve surgery or isolated valve surgery were more likely to experience post-operative AF compared with those who underwent isolated CABG (Log-Rank ptrend=0.0096). Among patients who were randomized to continuous cardiac rhythm monitoring, the probability of post-operative AF among patients who underwent isolated CABG, valve surgery, and CABG + valve surgery was 15.8%, 29.4%, and 35.0%, respectively (Log-Rank ptrend=0.017). After multivariable adjustment, the risk of developing post-operative AF within 30 days after discharge remained higher among patients who underwent valve surgery compared with those who underwent isolated CABG (hazard ratio (HR) 2.22, 95% CI 1.01–4.87. Patients who underwent CABG + repair/replacement had the highest risk of experiencing post-operative AF when compared to patients who underwent isolated CABG (HR 2.78, 95% CI 1.12–6.86). Conclusion Patients undergoing valve repair or bioprosthetic valve replacement have a substantial risk of post-operative AF within 30 days after discharge from surgery. An aggressive cardiac rhythm monitoring strategy during this vulnerable period should be considered for this high-risk patient population. Funding Acknowledgement Type of funding sources: Other. Main funding source(s): Heart and Stroke Foundation of Canada

The effect of cryothermic and radiofrequency Cox maze IV ablation on atrial size and function assessed by 3D echocardiography, a randomized trial. To freeze or to burn

Abstract Background The Cox maze procedures have been shown to be safe methods for restoring sinus rhythm (SR) in patient with atrial fibrillation and often performed concomitant to mitral valve (MV) surgery. Cryothermy (Cryo) and Radiofrequency (RF) are available techniques to achieve atrial linear scars. The differences between the effect of these energy sources on late left atrial (LA) reverse remodeling are not fully described. Purpose This study aims to compare the impact of Cryo and RF procedures on left atrial (LA) size and function one year after Cox-maze IV concomitant to MV surgery using 3-dimensional echocardiography (3DE). Methods Seventy-two patients with MV disease and atrial fibrillation were randomized to either Cryo (35) or RF (37) ablation. Another 33 patients were enrolled according to the protocol without concomitant ablation (NoMaze group). All patients had an echocardiogram before and one year after surgery. Results The 42 ablated patients who recovered sinus rhythm (SR) one year after surgery had comparable left and right systolic ventricular function and a mean reduction of LA size by 23% (LA volume index decreased from 66±24 to 54±13ml/m2, p=0.004). The 3DE extracted reservoir and booster function showed higher values after RF ablation compared to Cryo (37±10% vs 26±6%; p&amp;lt;0.001 resp. 18±9 vs 7±4%, p&amp;lt;0.001), while passive conduit function was comparable (24±11 vs 20±8%; p=0.17). Patients with restored SR without ablation had more preserved systolic atrial function but similar LA size reduction as those who underwent maze surgery. Conclusions SR restoration after MV surgery and maze results in LA size reduction irrespective of the energy source used. By 3DE we could show that, compared to RF maze, the extension of ablation area produced by Cryo implies a major LA structural remodeling affecting LA systolic function. The reverse size remodeling seems to be the least, the longer AF history. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): ALF funding for clinical research-Sweden

VALVULAR SURGERY IS ASSOCIATED WITH AN INCREASED RISK OF POST-OPERATIVE ATRIAL FIBRILLATION: SECONDARY ANALYSIS OF THE SEARCH-AF CARDIOLINK-1 RANDOMIZED TRIAL

VALVULAR SURGERY IS ASSOCIATED WITH AN INCREASED RISK OF POST-OPERATIVE ATRIAL FIBRILLATION: SECONDARY ANALYSIS OF THE SEARCH-AF CARDIOLINK-1 RANDOMIZED TRIAL

THE IMPACT OF STATIN ON POST-OPERATIVE ATRIAL FIBRILLATION AFTER DISCHARGE FROM CARDIAC SURGERY: SECONDARY ANALYSIS OF THE SEARCH-AF CARDIOLINK-1 RANDOMIZED TRIAL

THE IMPACT OF STATIN ON POST-OPERATIVE ATRIAL FIBRILLATION AFTER DISCHARGE FROM CARDIAC SURGERY: SECONDARY ANALYSIS OF THE SEARCH-AF CARDIOLINK-1 RANDOMIZED TRIAL

Machine learning prediction of atrial fibrillation in cardiovascular patients using cardiac magnetic resonance and electronic health information.

BackgroundAtrial fibrillation (AF) is a commonly encountered cardiac arrhythmia associated with morbidity and substantial healthcare costs. While patients with cardiovascular disease experience the greatest risk of new-onset AF, no risk model has been developed to predict AF occurrence in this population. We hypothesized that a patient-specific model could be delivered using cardiovascular magnetic resonance (CMR) disease phenotyping, contextual patient health information, and machine learning.MethodsNine thousand four hundred forty-eight patients referred for CMR imaging were enrolled and followed over a 5-year period. Seven thousand, six hundred thirty-nine had no prior history of AF and were eligible to train and validate machine learning algorithms. Random survival forests (RSFs) were used to predict new-onset AF and compared to Cox proportional-hazard (CPH) models. The best performing features were identified from 115 variables sourced from three data domains: (i) CMR-based disease phenotype, (ii) patient health questionnaire, and (iii) electronic health records. We evaluated discriminative performance of optimized models using C-index and time-dependent AUC (tAUC).ResultsA RSF-based model of 20 variables (CIROC-AF-20) delivered an overall C-index of 0.78 for the prediction of new-onset AF with respective tAUCs of 0.80, 0.79, and 0.78 at 1-, 2- and 3-years. This outperformed a novel CPH-based model and historic AF risk scores. At 1-year of follow-up, validation cohort patients classified as high-risk of future AF by CIROC-AF-20 went on to experience a 17.3% incidence of new-onset AF, being 24.7-fold higher risk than low risk patients.ConclusionsUsing phenotypic data available at time of CMR imaging we developed and validated the first described risk model for the prediction of new-onset AF in patients with cardiovascular disease. Complementary value was provided by variables from patient-reported measures of health and the electronic health record, illustrating the value of multi-domain phenotypic data for the prediction of AF.

The role of pacemaker algorithms in preventing atrial fibrillation progression

Background: Unnecessaryright ventricular (RV) pacing leads to cardiac dyssynchrony and increases the risk of developing permanent atrial fibrillation. Minimizing RV pacing by specefic algorithms decreases the AF risk. Aim and objectives: Our objective was to study the effect of pacemaker algorithms on atrial fibrillation progression. Subjects and Methods: Patients with dual chamber (group A) and single chamber (group B)pacemakers were included in the study. Patients with history of AF at the time of pacemaker implantation were not included in the study. The relation between pacemaker parameters and AF development was monitored. Result: Group A showed that RV pacing percentage had high significance for developing AF with P value P &lt;0.001, also A pacing had high significance for developing AF with P value &lt;0.001 and VIP mode OFF there was high significance of developing AF with P value &lt;0.001.As regards group B RV pacing (%) had high significant risk for developing AF with p value&lt;0.001,Also hysteresis off had high significant risk for developing AF with p value&lt;0.005. Conclusion: Reducing unnecessary RV pacing in single and dual chamber pacemakers is assossiated with decreasing the risk of AF.

Impact of atrioventricular junction ablation and CRT‐D on long‐term mortality in patients with left ventricular dysfunction, permanent, refractory atrial fibrillation, and narrow QRS: Results of a propensity‐matched analysis

In patients with symptomatic permanent atrial fibrillation (PEAF) and narrow QRS, atrio-ventricular junction ablation (AVJA) plus cardiac resynchronization therapy (CRT) is superior to medical therapy in reducing heart failure (HF) hospitalization and all-cause mortality. To compare the mortality of a population of patients with HF, reduced EF (rEF), and PEAF treated with AVJA plus CRT with that of a contemporary cohort of patients in sinus rhythm (SR) with similar baseline characteristics. In this prospective, multicentre, observational study, all-cause mortality in a group of consecutive patients undergoing AVJA and implantable cardioverter-defibrillator (ICD) combined with CRT implantation for HFrEF, narrow QRS, and PEAF with uncontrolled ventricular rate was compared with that of a contemporary cohort of patients in SR undergoing ICD implantation (not combined with CRT) for HFrEF and narrow QRS. Individual 1:1 propensity matching of baseline characteristics was performed. A total of 824 patients were enrolled. Propensity matching yielded 107 matched pairs. After a median follow-up of 52 months, all-cause mortality was similar in patients treated with AVJA plus CRT and in the control group (p = .434). In AVJA plus CRT patients, mortality was significantly lower than in control group patients with a history of paroxysmal/persistent AF (n = 45, p = .020), and similar to that of patients without a history of AF (n = 62, p = .459). After adjustment for patient characteristics, the long-term prognosis of patients with HFrEF, narrow QRS, and PEAF who underwent AVJA plus CRT was similar to that of a population of patients in SR with similar characteristics.

A worsened prognosis for patients after a stroke with newly diagnosed atrial fibrillation compared to having a preexisting arrhythmia.

IntroductionAtrial fibrillation (AF) is a major cause of the ischemic stroke. Patients with undiagnosed AF lack the stroke prevention provided by oral anticoagulants. The aim of this study was to compare the in-hospital mortality rate between ischemic stroke patients diagnosed with AF de novo against ischemic stroke patients diagnosed with AF prior to hospitalization for stroke.Material and methodsWe identified patients admitted to the Neurology Center during the years 2013-2014 with acute ischemic stroke and AF. We analyzed in-hospital outcomes in patients with newly diagnosed AF and those with known AF. The study endpoint was death during hospitalization.ResultsThe study included 2,000 patients with acute ischemic stroke out of which 579 patients (29%) were diagnosed with AF. AF was newly diagnosed in 123 patients (21.2%) (new-AF group), while 456 patients (78.8%) had a history of AF (previous-AF group). Mean National Institutes of Health Stroke Scale (NIHSS) score at admission was 7.2 points in the new-AF group and 3.7 in previous-AF group (P&lt;0.001). In-hospital death was more common in new-AF group (13 patients, 10.6%) than in previous-AF group (16 patients, 3.5%) (P=0.003). In multivariate analysis, the NIHSS score at admission in new-AF group was associated with higher mortality, while in previous-AF group, the NIHSS score at admission and multiple ischemic foci were risk factors of in-hospital mortality.ConclusionsNewly diagnosed AF in ischemic stroke patients significantly worsens prognosis compared to patients previously diagnosed with AF. Early detection of latent AF and subsequent use of anticoagulation is important in preventing severe stroke.

Epidemiology of subclinical atrial fibrillation in patients with cardiac implantable electronic devices: A systematic review and meta-regression

BackgroundIn recent years, attention to subclinical atrial fibrillation (SCAF), defined as the presence of atrial high-rate episodes (AHREs), in patients with cardiac implantable electronic devices (CIEDs), has gained much interest as a determinant of clinical AF and stroke risk. We aim to perform a systematic review and meta-regression of the available scientific evidence regarding the epidemiology of SCAF in patients receiving CIEDs. MethodsPubMed and EMBASE were searched for all studies documenting the prevalence of AHREs in patients (n=100 or more, <50% with history of AF) with CIEDs from inception to 20th August 2021, screened by two independent blind reviewers. This study was registered in PROSPERO: CRD42019106994. ResultsAmong the 2614 results initially retrieved, 54 studies were included, with a total of 72,784 patients. Meta-analysis of included studies showed a pooled prevalence of SCAF of 28.1% (95%CI: 24.3-32.1%), with high heterogeneity between studies (I2=98%). A multivariable meta-regression was able to explain significant proportion of heterogeneity (R2=61.9%, p<0.001), with age and follow-up time non-linearly, directly and independently associated with occurrence of SCAF. Older age, higher CHA2DS2-VASc score, history of AF, hypertension, CHF, and stroke/TIA were all associated with SCAF occurrence. ConclusionsIn this systematic review and meta-regression analysis, SCAF was frequent among CIED recipients and was non-linearly associated with age and follow-up time. Older age, higher thromboembolic risk, and several cardiovascular comorbidities were associated with presence of SCAF.

Short term outcomes of distal (ventricular) His bundle pacing: A single centre retrospective study

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Chronic right ventricular apical pacing can lead to pacing induced cardiomyopathy in a significant proportion of patients. Conduction system pacing may restore more physiological activation of the heart, and has recently been shown to have favourable outcomes in clinical trials. However there remains concern regarding the long-term outcomes due to lead displacement and high pacing thresholds. The most widely used technique in current practice is to pace the His bundle proximal to the tricuspid valve. Distal His bundle pacing has a number of advantages over proximal His pacing, including, lower capture thresholds, a more stable lead position, less far field atrial sensing and better spacing from the AV node in case ablation of this is required for AF rate control. Despite these, outcomes of distal His bundle pacing from the ventricular aspect are less well defined. Methods We performed a retrospective review of patients who underwent conduction system pacing between January 2020 and October 2021 at our centre. During this period all procedures were performed employing a distal His bundle pacing approach with the lead placed on the ventricular aspect of the tricuspid annulus. Data was collected at implant, follow-up at 1 month and then every 6 months. Results Out of 35 patients, 33 underwent successful His bundle pacing (acute success rate of 94%), 1 patient had left bundle branch pacing and another patient had an unsuccessful procedure. Mean age was 74 years, median LVEF 45% and median pre-implant QRS was 108ms. 80% of the cohort had a history of AF. The indications for pacing were as follows: AF - for pace &amp; ablate (60%); high grade AV block with narrow QRS and mild LVSD (17%); failed LV lead (14%); and other 9%. Mean procedure duration and fluoroscopy time were 78 minutes and 12.05 minutes, respectively. Median threshold at implant was 1.00V (IQR 0.719V). Selective His bundle pacing was achieved in 60% and non-selective in 34%. Mean follow-up duration was 150 days with median threshold at last f/up of 0.75V (IQR 0.750V). There were no acute procedural complications. 1 patient had a significant rise in threshold at follow-up and therefore required upgrade to CRT-P. Discussion Our data shows that distal His bundle pacing is a safe and effective technique for conduction system pacing. Thresholds appear stable at follow-up and failure rate was found to be comparable to biventricular pacing. We noted an initial learning curve for both implanter and physiologists with relatively poorer outcomes for the earlier cases. Longer term follow-up is ongoing, including functional assessment and follow-up to assess for remodelling with echocardiography. Prospective randomised trials are needed to compare conduction system pacing vs RV pacing in AF patients with HFpEF or mild LVSD undergoing AVN ablation, and vs biventricular pacing in the severe LVSD population.

Atrial fibrillation is associated with an increased risk of ventricular arrhythmias and sudden death in patients with pacemakers and implantable cardioverter defibrillators (ICDs)

Abstract Funding Acknowledgements Type of funding sources: None. Background Atrial fibrillation (AF) has been linked to an increase in the risk of ventricular arrhythmias. Purpose We aimed to investigate whether AF is associated with an increased risk of ventricular tachycardia (VT), ventricular fibrillation (VF) and sudden death (SD) in patients with cardiac implantable electronic devices (CIEDs). Methods All patients hospitalised in France between 2011 and 2020 with a history of pacemakers (PPMs) and implantable cardioverter defibrillator (ICD) were identified from the French National database. Patients with a prior history of VT, VF and SD were excluded. Results A total of 701,195 patients were identified. Of these, 581,781 (90.1%) patients had PPMs and 63,726 (9.9%) had ICDs. In the PPM group, 248046 (42.6%) had AF and 333735 (57.4%) had no AF. After multivariable analysis, predictors for VT, VF and SD included sex, diabetes, heart failure, history of pulmonary oedema, valve disease, dilated cardiomyopathy, coronary artery disease (CAD), AF, vascular disease, intracranial bleeding, smoking, dyslipidaemia, alcohol related disorders, lung disease, chronic kidney disease (CKD), thyroid disorders, inflammatory diseases, anaemia, poor nutrition, cognitive impairment, previous cancer and frailty. The incidence of VT, VF and SD was higher in patients with AF (1.47%/year) compared to those without AF (0.94%/year), with the risk significantly elevated in the former group, hazard ratio (HR) 1.554 (confidence interval (CI) 1.508-1.601). After adjustment for confounders (Figure 1), AF was still associated with a significantly increased risk of VT, VF and SD, HR 1.236 (CI 1.198-1.276) in patients with PPMs. This was further demonstrated through a 1:1 propensity score matched (PSM) analysis (n=200977 in each group) where the risk of incident outcomes was significantly higher in PPM patients with AF, HR 1.230 (1.187-1.274), compared to those without AF. In the ICD group, 20965 (32.9%) had AF and 42761 (67.1%) had no history of AF. Predictors of VT, VF and SD after multivariable analysis included age, sex, diabetes mellitus, heart failure, valve disease, CAD, previous percutaneous coronary intervention, vascular disease, AF, CKD, liver disease and frailty. Incidence of VT, VF and SD was higher in ICD patients with AF (5.30%/ year) compared to those without AF (4.21%/year), with a significantly higher risk, HR 1.261 (CI 1.204-1.320). After adjustment for confounders, this elevated risk was still significant HR 1.167 (1.111-1.226) (Figure 1). 1:1 PSM analysis (n=18349 in each group) demonstrated this further with a significantly elevated risk in ICD patients with AF, compared to ICD patients without AF, HR 1.134 (CI 1.071-1.200). Conclusion Our findings suggest that patients with PPM and ICD with concurrent AF are at a higher risk of VT, VF and sudden death compared to patients with PPM and ICD who do not have AF.

Prediction of thrombosis in atrial fibrillation with compact atrial shape representation

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): IHU LIRYC ANR-10-IAHU-04 ERACoSysMed PARIS Project Background The impact of LA shape on clot formation in AF is yet to be understood Purpose To analyze the impact of LA, PVs and LAA orientations on clot formation Methods Pts with history of AF and an indication for LAA closure underwent pre-operative cardiac CT. Those with either a prior history of embolism or a clot detected on arterial and venous-enhanced CT images were categorized as clot positive. On CT images, the LA was segmented and meshed. Automated labelling of PVs and LAA was employed to build a compact skeleton representation of the LA (by registering labels from a template to all cases, and by connecting the center of mass of each labels). LA skeletons were used to train a novel Neural Network model for joint classification of heterogeneous data, such as images taken at different phases of the cardiac cycle. Such model consists of one encoder per dataset followed by a common classifier, enforcing a joint representation of all datasets in the same latent space. This is made possible by writing the task as a variational problem to optimise, we call this model a multi-channel variational classifier. The model was trained to predict clot positive patients and its generalizability was assessed on a test population. Results 237 pts were included (age 74±8, 70% males, CHADS-VASc 4.3±1.2). CTs were acquired during systole in 117 and diastole in 120. 100 (42%) patients were considered clot positive. Segmentation, labeling and skeletization was successfully achieved in all pts. The model was trained using a 10-Fold cross validation. We compared the results after training on diastole and systole cases independently and by jointly training on both datasets. At testing, our model reached a 0.72 overall accuracy for the prediction of LAA clots (0.83 for systole and 0.61 for diastole), while training separately on systole and diastole was prone to strong overfitting and mode collapse with 0.52 and 0.48 accuracy, respectively. Conclusion While LA shape, LA size, PV and LAA orientations alone may not be sufficient for robust clot prediction, we introduce a compressed representation of the global anatomy that closely relates to LAA thrombosis, possibly identifying global features related to adverse hemodynamics. The method is reproducible and introduces a novel approach to accommodate heterogeneous diastole and systole datasets.

Real-world experience on implantation and atrial signal detection of a SC ICD with atrial sensing capability: The MATRIX study

Abstract Funding Acknowledgements Type of funding sources: Private company. Main funding source(s): BIOTRONIK, Berlin, Germany Introduction A single-lead implantable cardioverter-defibrillator (ICD) with atrial sensing dipole (the DX ICD system) can potentially give additive information concerning atrial diagnostics in patients requiring only a single-chamber ICD. We therefore report the real-world experience from large DX registry on implantation, atrial signal quality and detection and the long-term stability of the atrial signal. Methods The prospective, single-arm MATRIX (Management and Detection of Atrial Tachyarrhythmias in Patients Implanted With BIOTRONIK DX Systems, NCT01774357) registry study effectively enrolled 2041 patients at 119 sites in 24 countries. All patients had a DX system implanted for a single-chamber ICD indication for primary or secondary prevention of sudden cardiac death. Patients were followed for 24 months including remote monitoring. Implantation and follow-up data are reported for the whole patient set. For the analyses on atrial sensing amplitude values, remotely transmitted device measurements of patients without history of long-standing persistent or permanent AF at baseline were used. Results The mean follow-up period was 677±173 days. Implantation took place at 15±22 days before enrollment. Baseline and implantation data are shown in the table. Implantation procedure and lead insertion were rated as "easy" or "very easy" in 91.0% and 96.3% of assessments, respectively. At implantation, the investigators rated the quality of the atrial sensing amplitude as "sufficient" in 97% of the assessed cases. At enrollment (12-month/24-month follow-up), the atrial signal quality and detection were rated as "good" or "excellent" in 92.3% (89.8%/89.9%) and 92.4% (90.1%/91.3%) of assessments, respectively. For 1841 patients (90.2%), remotely transmitted device information was received. The median (mean ± SD, IQR) transmission rate was 92.5% (85.4±18.2%, 81.4-97.3%). 1746 patients (85.5%) matched the inclusion criteria for the quantitative analyses on atrial sensing. 95.6% of available RA sensing amplitude values were ≥1 mV. Based on each patient’s overall median value, the median (mean ± SD, IQR) RA sensing amplitude was 4.6 mV (4.4±2.0 mV, 2.8-6.2 mV). The time course of patient median values stratified by month is shown in the figure. Conclusion The study followed 2041 patients implanted with the DX ICD system for two years. In the vast majority of cases, investigators rated implantation as (very) easy and the atrial signal over 24 months as good/excellent. According to daily, automatic Home Monitoring data, the overall mean P-wave amplitude remained stable throughout the whole follow-up. The MATRIX study demonstrated functionality and clinical utility of the DX concept in an unselected, real-life setting.

Differential sodium current remodelling in human left atrial appendage cardiomyocytes in paroxysmal and persistent atrial fibrillation

Abstract Funding Acknowledgements Type of funding sources: None. Background Atrial fibrillation (AF) is characterized by complex electrical, structural and metabolic remodelling. The mechanisms underlying AF progression from paroxysmal to persistent AF are not fully understood, and studies in cardiomyocytes (CMs) at the paroxysmal stage of AF are lacking. Moreover, most studies have so far investigated right atrial appendage CMs, while left atrial appendage (LAA) CMs may be more informative, as AF is predominantly a left atrial disease. Whether and to what extent electrical remodelling during various AF stages also includes alterations of the (late) sodium current (INa), remains unclear. Moreover, the functional relevance of sodium channel isoforms other than the cardiac Nav1.5, such as the "neuronal" isoform SCN10A/NaV1.8, during the various stages of AF is as yet not fully elucidated. Purpose To investigate peak and late INa remodelling in LAA CMs from patients with paroxysmal and persistent AF and patients in sinus rhythm (SR), as well as the potential contribution of NaV1.8-based current. Methods LAA were obtained from patients in SR (N=18) without a history of AF undergoing cardiac surgery, as well as from patients with paroxysmal (N=12) and persistent AF (N=30). Paroxysmal AF was defined as AF episodes terminating spontaneously within seven days and persistent as AF continuing for more than 7 days but less than 1 year. Peak INa, late INa and action potential (AP) properties were investigated through patch-clamp analysis on single LAA CMs, while qPCR was used to assess SCN5A and SCN10A expression levels in LAA tissue. Results In paroxysmal and persistent AF CMs, AP duration was shorter than in SR CMs. Compared to SR, peak INa (Figure 1A) and SCN5A expression (Figure 1B) were significantly decreased in paroxysmal AF, while they were restored to SR levels in persistent AF. Conversely, while late INa was undetectable in SR and paroxysmal AF, it was significantly increased in persistent AF (Figure 2). Peak and late INa Nav1.8-based current was not detected in persistent AF CMs. Similarly, expression of SCN10A was not observed in LAAs at any stage. Conclusions Our study is the first to show that AP shortening already occurs in LAA CMs from paroxysmal AF, potentially contributing to pro-arrhythmia in this early stage of the disease. Moreover, our findings demonstrate that INa is differentially remodelled during various stages of AF, with peak INa reduction occurring during paroxysmal AF, while late INa is increased in persistent AF only. Finally, we have shown that Nav1.8 current does not contribute to the AF-related alterations in INa. These observations are of particular relevance when considering potential pharmacological approaches targeting (late) INa in patients with distinct forms of AF.