Subsequent Atrial Fibrillation Research Articles

Atrial Fibrillation (AF) detected by repeat handheld ECG screening and the risk of heart failure hospitalization

Abstract Purpose Heart failure and atrial fibrillation (AF) frequently complicate one another. Risk of heart failure in screen-detected patients was not investigated. We aimed to compare risk of hospitalization for heart failure (HHF) between screen-detected and clinically-diagnosed AF, and to evaluate the impact of AF burden. Methods Consecutive patients aged over 65 attending outpatient clinics were prospectively recruited for AF screening, using handheld single-lead ECG (AliveCor) during December 2014 and December 2017. Patients who had >1 visits received repeat screening. All participants were divided into 5 cohorts: (i) previously known AF at enrolment; (ii) initial screen-detected AF; (iii) subsequent screen-detected AF; (iv) clinically-diagnosed AF during follow-up (FU); (v) No AF. Risk of HHF was estimated by adjusted sub-distribution hazard ratios (aSHR) derived from Fine and Gray regression, accounting for death as competing risk, adjusting for CHA2DS2VASC components and chronic kidney disease, AF diagnosis being handled as time-dependent variable. Patients who participated in repeat screening and previously known AF formed a sub-cohort. Patients with previously known AF who were in AF in the initial screening and those with repeat screen-positivity were defined probably persistent AF, otherwise paroxysmal AF (single screen-positivity) or no AF (never screen-positive). Risk of HHF was compared between groups stratified by AF burden (persistent vs. paroxysmal) and scenario of AF diagnosis (screen-detected vs. clinically-diagnosed). Results Of 11,972 subjects (mean age 76.6±7.8, female 49.2%), 18.7% (n=2,236) had known AF, 1.9% (n=223) initial screen-detected AF, 0.6% (n=71) subsequent screen-detected AF, 7.3% (n=867) clinically-diagnosed AF during FU, and 71.6% (n=8,559) no AF. During a median FU of 6.7 (IQR:4.4-8.0) years, risk of HHF was highest in patients with clinically-diagnosed AF (aSHR=3.5(2.7-4.5)), followed by subsequent screen-detected AF (aSHR=2.8(1.6-5.0)), previously known AF (aSHR=1.9(1.6-2.2)), and initial screen-detected AF (aSHR=1.7(1.1-2.4)) (Figure 1a). Sensitivity analysis excluded those with known heart failure at baseline, after which risk of HHF became comparable between previously known and initial screen-detected AF (Figure 1b). Sub-analysis for participants (32.2% (n=3,853), mean age 76.7±7.3, female 47.5%) of repeat screening showed screen-detected persistent AF (aSHR=3.7(1.9-7.2)) was at highest risk of HHF, followed by clinically-diagnosed AF (AF burden unassessed) (aSHR=3.3(2.2-5.0)), previously known persistent AF (aSHR=3.1(2.5-3.8)), screen-detected paroxysmal AF (aSHR=2.1(1.4-3.4)), previously known paroxysmal AF (aSHR=1.8(1.3-2.4) (Figure 1c). Conclusion Higher AF burden and FU new AF diagnosed by either screening or clinic visit was associated with higher risk of HHF. Screening facilitating early AF diagnosis and early downstream intervention, warranted further study.

Screening for Atrial Fibrillation (AF) by handheld single-lead ECG and risk of all-cause mortality stratified by non-AF cardiovascular disease

Abstract Purpose Screening for Atrial fibrillation (AF) has been suggested as a strategy to increase early detection of silent AF. We aimed to evaluate all-cause mortality between patients with screen-detected and clinically-diagnosed AF, and the effect of oral anticoagulation therapy (OAC) on mortality. Methods We prospectively enrolled and performed AF screening using handheld single-lead ECG(AliveCor) on consecutive patients who attended medical outpatient clinics during December 2014 and December 2017. Repeat screening was performed among patients who had >1 clinic visits. All participants were divided into 5 cohorts: (i) previously known AF at baseline (kAF); (ii) initial screen-detected AF (S1-AF); (iii) subsequent screen-detected AF (FU-sAF); (iv) clinically-diagnosed AF during follow-up (FU-cAF); and (v) no AF. Risk of all-cause mortality was estimated by adjusted hazard ratio (HR) using COX proportional hazards regression, adjusting for age, gender, co-morbidities, concurrent chronic use of medications including OAC, with AF detection or clinical diagnosis and OAC therapy handled as time-varying variable. Subgroup analysis was conducted to identify heterogeneity of effect across with or without non-AF cardiovascular disease (CVD). Results Of 11,972 subjects (mean age 76.6±7.8, female 49.2%), 18.7% (n=2,236) had previously kAF, 1.9% (n=223) S1-AF, 0.6% (n=71) FU-sAF, 7.3% (n=867) FU-cAF, and 71.6% (n=8,559) no AF. During a median FU duration of 6.8(IQR: 5.2-8.1) years, patients with kAF (HR=1.8(1.6-2.0)), S1-AF (HR=1.6(1.3-1.9)) and FU-cAF (HR=1.6(1.4-1.8)) were at higher risk of all-cause mortality, compared to individuals without AF, whereas FU-sAF (HR=1.0(0.7-1.4)) had similar low risk of death as no AF. Heterogeneity of effect was detected in subgroup analysis. Among patients without non-AF CVD, FU-sAF (HR=6.0(1.8-19.8)) and FU-cAF (HR=4.7(3.3-6.7)) were at markedly higher risk of all-cause mortality. DOAC (HR=0.57(0.38-0.87)) but not VKA (HR=0.72(0.43-1.15) reduced mortality. However, in patients with CVD other than AF, risk of FU-sAF (HR=1.1(0.8-1.6)) decreased to as low as individuals without AF (P for interaction =0.0039).Both DOAC (HR=0.51(0.46-0.58)) and VKA (HR=0.87(0.78-0.98) were beneficial. Conclusion Likely delayed AF detection suggested by groups of FU-cAF and FU-sAF may be associated with significant rise in risk of mortality among patients without non-AF CVD. The effect diminished when non-AF CVD as potential competing risk existed. The role of VKA in reducing all-cause mortality warrants more studies.

The Usefulness of Outpatient Cardiac Telemetry in Patients with Cryptogenic Stroke.

Introduction: Atrial fibrillation (AF), apart from non-stenotic supracardiac atherosclerosis and neoplastic disease, is the leading cause of cryptogenic stroke, including embolic stroke of un-determined source (ESUS). The aim of our study was to determine the prevalence of AF in ESUS patients based on 30-day telemetric heart rate monitoring initiated within three months after stroke onset. Another aim was to identify factors that increase the likelihood of detecting subsequent AF among ESUS patients. Material and Methods: patients with first-ever stroke classified as per the ESUS definition were eligible for this study. All patients underwent outpatient 30-day telemetric heart rate monitoring. Results: In the period between 2020 and 2022, 145 patients were included. The mean age of all qualified patients was 54; 40% of eligible patients were female. Six patients (4.14%), mostly male patients (4 vs. 2), were diagnosed with AF within the study period. In each case, the diagnosis related to a patient whose stroke occurred in the course of large vessel occlusion. Episodes of AF were detected between day 1 and 25 after starting ECG monitoring. Out of the analyzed parameters that increase the probability of, A.F.; only supraventricular extrasystoles proved to be an independent factor regarding an increased risk of AF [OR 1.046, CI 95% 1.016-1.071, p-value < 0.01]. Conclusions: The use of telemetry heart rhythm monitoring in an outpatient setting can detect AF in 4% of ESUS patients who have undergone prior diagnostic procedures for cardiogenic embolism. Supraventricular extrasystoles significantly increases the likelihood of AF detection in patients with ESUS within three months following stroke. Comorbid coronary artery disease, diabetes and hypertension, rather than a single-factor clinical burden, increase the likelihood of AF detection in older ESUS patients. ESUS in the course of large vessel occlusion is probably associated with an increased likelihood of cardiogenic embolism.

Post-operative atrial fibrillation after noncardiac surgery: diagnostic role of ambulatory rhythm monitoring for recurrent arrhythmia after hospital discharge

Abstract Introduction Postoperative atrial fibrillation (POAF) after noncardiac surgery constitutes 10-15% of all cases of incident atrial fibrillation (AF) in the community and has been associated with an increased risk of stroke. The risk of subsequent AF among patients with POAF is not well defined. Purpose To evaluate the role of systematic 30-day electrocardiographic (ECG) monitoring in the detection of AF recurrence after POAF. Methods In a prospective interventional study, patients who underwent major noncardiac surgeries and had new AF documented by ECG in the post-operative period between May 2022 and April 2023 were identified. For these patients, a 30-day ambulatory ECG monitor was recommended upon discharge, with final ordering deferred to the primary inpatient teams. Rates of recurrent AF of any duration detected by 30-day monitoring plus routine care versus routine care alone after the surgery were compared. Results Eighty-five patients with new-onset POAF were included (mean age 72 years, male 67%). Of these, 35 (41%) patients underwent up to 30 days [median 23 (IQR 6-27) days] of continuous ECG monitoring after hospital discharge. There were no significant differences in baseline characteristics between patients who did or did not undergo monitoring (Table 1). During median 281 (IQR 197-385) days of follow-up, recurrent AF was documented in 14/35 (40%) patients in the monitoring group as opposed to 7/50 (14%) patients in the usual care group (log-rank p=0.003, Figure 1). The median time from day of surgery until documented AF recurrence was 25 (IQR 6-53) days in the monitoring group and 66 (IQR 25-145) in the usual care group. Overall, 81% of recurrent AF events in both groups were detected in the first 3 months after surgery. The median burden of AF in the cardiac monitoring group was 7% (IQR 1-15), with the longest AF event lasting a median of 6 (IQR 2-18) hours. Anticoagulation for AF was prescribed in 24/64 (37%) patients with POAF without recurrence and in 16/21 (76%) patients with recurrent AF. Conclusion Recurrent AF following POAF is common and detected most frequently in the first 3 months after noncardiac surgery. Systematic ambulatory rhythm monitoring is associated with a higher rate of AF detection following hospital discharge and may identify a patient subgroup who might benefit from anticoagulation therapy.Table 1Figure 1

Effects of Glucagon-Like Peptide-1 Receptor Agonists on Atrial Fibrillation Recurrence After Catheter Ablation

BackgroundRelationship between glucagon-like peptide-1 receptor agonist (GLP-1 RA) use prior to atrial fibrillation (AF) ablation and subsequent AF recurrence is not well-understood. ObjectivesThis study investigated the effects of GLP-1 RA use within 1 year before ablation and its association with AF recurrence and associated outcomes. MethodsThe TriNetX research database was used to identify patients aged ≥18 years undergoing AF ablation (2014-2023). Patients were categorized into 2 groups, and propensity score matching (1:1) between preablation GLP-1 RA users and nonusers was performed based on demographics, comorbidities, body mass index, laboratory tests, AF subtype, and medications. Primary outcome was composite of cardioversion, new antiarrhythmic drug therapy, or repeat AF ablation after a 3-month blanking period following the index ablation. Additional outcomes included ischemic stroke, all-cause hospitalization, and mortality during 12-month follow-up period. ResultsAfter 1:1 propensity score matching, the study cohort comprised 1,625 GLP-1 RA users and 1,625 matched GLP-1 RA nonusers. Preablation GLP-1 RA therapy was not associated with a lower risk of cardioversion, new AAD therapy, and repeat AF ablation after the index procedure (HR: 1.04 [95% CI: 0.92-1.19]; log-rank P = 0.51). Furthermore, the risk of ischemic stroke, all-cause hospitalization, and mortality during the 12-month follow-up period did not differ between the 2 groups. ConclusionsThese findings suggest that preprocedural use of GLP-1 RAs is not associated with a reduced risk of AF recurrence or associated adverse outcomes following ablation, and underscore the need for future research to determine whether these agents improve outcome in AF patients.

Complex left appendage morphology is associated with Embolic Stroke of Undetermined Source.

Variations in the left atrial appendage (LAA) morphology are associated with different embolic risk in patients with atrial fibrillation (AF). Data are scarce regarding the association between LAA morphology and Embolic stroke of undetermined source (ESUS). Using cardiac computed tomography (CCT) scans, LAA morphology was categorized as either chicken wing (CW), cactus, windsock, or cauliflower. Furthermore, we examined the presence of large secondary lobes arising from the main lobe, considering their existence as indicative of a complex LAA morphology. LAA morphologies were compared between ESUS (n = 134) and AF patients (n = 120); and between ESUS patients with (n = 24) and without (n = 110) subsequent AF diagnosis during long-term follow-up. ESUS patients had a significantly higher prevalence of cauliflower morphology compared to AF group (52% vs 34%, respectively, p = 0.01); however, no significant difference was found between the groups when categorizing LAA morphology to either CW or non-CW. ESUS patients had significantly higher prevalence of large secondary lobes compared with AF patients (50% vs 29%, respectively, p = 0.001). When comparing ESUS patients with and without AF diagnosis during follow-up (20-48 months of follow-up, median 31 months), there were no significant differences in the prevalence of the "classical" morphologies, but large secondary lobes were significantly more prevalent among those without subsequent AF diagnosis. ESUS patients have a high prevalence of complex LAA morphology, which might be associated with an increased risk for thrombus formation even in the absence of AF.

Insomnia symptoms and risk for atrial fibrillation - The HUNT study.

Studies on the effect of insomnia on atrial fibrillation risk in the general population are limited, therefore we investigated the association between insomnia and the risk of atrial fibrillation in a large-scale population-based study with valid atrial fibrillation measure. A total of 33,983 participants (55% women) reported their insomnia symptoms in the third wave of the HUNT study (between 2006 and 2008) in Norway, and they were followed for their first atrial fibrillation diagnosis until 2020 using hospital registers. Atrial fibrillation diagnoses were validated by physicians based on medical records and electrocardiograms. Insomnia symptoms were assessed by four questions, and analysed both individually and as cumulative symptoms. Cox regression, adjusted for age, sex, social and marital status, working in shiftwork, alcohol consumption, smoking, physical activity, body mass index, systolic blood pressure, and symptoms of anxiety and depression, was conducted. Overall, 1592 atrial fibrillation cases were identified during the follow-up and 31.6% of individuals reported at least one insomnia symptom. In our analysis, we did not detect meaningful associations between insomnia symptoms and the risk of atrial fibrillation. In conclusion, in this population there was no evidence for an association between insomnia symptoms and the risk of subsequent atrial fibrillation.

Robust Artificial Intelligence Tool for Atrial Fibrillation Diagnosis: Novel Development Approach Incorporating Both Atrial Electrograms and Surface ECG and Evaluation by Head-to-Head Comparison With Hospital-Based Physician ECG Readers.

Atrial fibrillation (AF) increases risk of embolic stroke, and in postoperative patients, increases cost of care. Consequently, ECG screening for AF in high-risk patients is important but labor-intensive. Artificial intelligence (AI) may reduce AF detection workload, but AI development presents challenges. We used a novel approach to AI development for AF detection using both surface ECG recordings and atrial epicardial electrograms obtained in postoperative cardiac patients. Atrial electrograms were used only to facilitate establishing true AF for AI development; this permitted the establishment of an AI-based tool for subsequent AF detection using ECG records alone. A total of 5 million 30-second epochs from 329 patients were annotated as AF or non-AF by expert ECG readers for AI training and validation, while 5 million 30-second epochs from 330 different patients were used for AI testing. AI performance was assessed at the epoch level as well as AF burden at the patient level. AI achieved an area under the receiver operating characteristic curve of 0.932 on validation and 0.953 on testing. At the epoch level, testing results showed means of AF detection sensitivity, specificity, negative predictive value, positive predictive value, and F1 (harmonic mean of positive predictive value and sensitivity) as 0.970, 0.814, 0.976, 0.776, and 0.862, respectively, while the intraclass correlation coefficient for AF burden detection was 0.952. At the patient level, AF burden sensitivity and positive predictivity were 96.2% and 94.5%, respectively. Use of both atrial electrograms and surface ECG permitted development of a robust AI-based approach to postoperative AF recognition and AF burden assessment. This novel tool may enhance detection and management of AF, particularly in patients following operative cardiac surgery.

The value of serial echocardiography in risk assessment of patients with paroxysmal atrial fibrillation.

Progression from paroxysmal to persistent atrial fibrillation (AF) is associated with increased morbidity and mortality. We examined the association of left atrial (LA) remodeling by serial echocardiography, and AF progression over an extended follow-up period. Two-hundred ninety patients (mean age 61 ± 11years, 73% male) who underwent transthoracic echocardiography performed at first presentation for non-valvular paroxysmal AF (PAF) and repeat echocardiogram 1-year later, were followed for progression to persistent AF. LA and left ventricular (LV) dimensions, volumes, LA reservoir, conduit and booster pump strains, LV global longitudinal systolic strain (GLS) assessedby 2D speckle tracking, and PA-TDI (time delay between electrical and mechanical LA activation- reflecting the extent of LA fibrosis) were compared on serial echocardiography. Sixty-nine (24%) patients developed persistent AF over a mean follow-up period of 6.3years. At baseline, patients with subsequent persistent AF had larger LA dimensions (46mm vs. 42mm, p < 0.001), indexed LA volumes (41ml/m2 vs. 34ml/m2, p < 0.001), lower LA reservoir and conduit strain (17.6% vs. 27.6%, p < 0.001; 10.5% vs. 16.3%, p < 0.001; respectively) and longer PA-TDI (155ms vs. 132ms, p < 0.001) compared to the PAF group. Patients with subsequent persistent AF showed over time significant enlargement in LA volumes (from 37.7ml/m2 to 42.4ml/m2, p < 0.001), lengthening of PA-TDI (from 142.2ms to 162.2ms, p = 0.002), and decline in LA reservoir function (from 21.9% to 18.1%, p = 0.024) after adjusting for age, gender, diabetes and LV GLS. There were no changes in LA diameter, LA conduit or booster pump function. Conversely, the PAF group showed no decline in LA function. Patients who developed persistent AF had larger LAsize and impaired LA function and atrial conduction times at baseline, compared to patients who remained PAF. Over the 1-year time course of serial echocardiographic evaluation, there was progression of LA remodeling in patients who subsequently developed persistent AF, but not in patients who remained inPAF.

Echocardiographic predictors of occult atrial fibrillation in patients with cryptogenic stroke

Abstract Background Left atrial (LA) strain has been proposed as an echocardiographic predictor of subsequent atrial fibrillation (AF) in patients presenting with cryptogenic stroke (CS). The purpose of this study was to compare the predictive value of LA strain parameters with traditional echocardiographic measurements for predicting occult AF in patients with CS. Methods We conducted a single-center retrospective cohort study of patients with cryptogenic stroke who underwent implantable cardiac monitor (ICM) placement. Transthoracic echocardiogram (TTE) parameters collected included mitral e and e’ velocities, and LA volume index (LAVI). LA strain was calculated offline using speckle-tracking in apical 4 and 2 chamber views, during the reservoir, conduit, and contractile phases of the cardiac cycle. Strain measurements obtained in each view were averaged (Figure 1). AF episodes had to last at least 2 minutes to qualify as an AF event. Results The cohort consisted of 269 patients with cryptogenic stroke who underwent ICM placement between April 2015 to December 2020, of them 45 patients had AF detected by ICM during follow-up. Echocardiographic evidence of dilated LA measured using LAVI (p=0.043) as well as lower filling pressures measured using e/e’ (p=0.033) were significantly associated with AF. (Table 1). LA function using strain in reservoir, conduit, and contractile phases was not significantly associated with AF (Table 1). Conclusion Increased LA size, but not abnormal LA function was significantly associated with incident AF in patients with CS.

Abstract 14114: An Extreme Case of Calcific Constrictive Pericarditis

Introduction: Constrictive pericarditis (CP) can lead to cardiac dysfunction and a range of clinical symptoms. However, differentiating it from conditions like restrictive cardiomyopathy can be challenging due to the overlapping features. Case Presentation: We present a case of a 61-year-old female with a history of atrial flutter and subsequent atrial fibrillation, experiencing worsening dyspnea on exertion, lip cyanosis, and upper abdominal constriction. Extensive diagnostic workup, including Echo, CT scan, and cardiac MRI, revealed severe biatrial enlargement, ventricular interdependence, elevated filling pressures, reduced cardiac output, and extensive pericardial thickening and calcifications ( Figures 1.a and 1.b ). These findings supported the diagnosis of extensive CP. Discussion: CP is often missed and delayed in diagnosis due to its complex hemodynamics and the non-specific symptoms. Typically, the initial imaging modality to be performed is an Echo. Specific findings such as dilated vena cava, preserved tissue velocity with annuls paradoxus, abnormal respiratory septal shift, and respiratory variations in mitral/tricuspid inflow should be first clues for potential diagnosis. Furthermore, evaluation of the hepatic vein with diastolic flow reversal during expiration is a key finding. Lack of respiratory variation in the SVC is also important. Cardiac CT will assess pericardial thickness and calcification, while cardiac MRI is key for the diagnosis by showing the pericardial thickness and fibrosis as well as the septal respiratory shift and venous congestion. An invasive hemodynamic study might be required if imaging is inconclusive. this patient’s presentation, imaging findings, exercise test results and collectively supported considering radical pericardiectomy. Conclusions: This report highlights the diagnostic challenges related to CP and the importance employing a multimodality imaging approach for accurate diagnosis.

Abstract 13928: Targeted Atrial Inhibition of Galphaq Signaling With Inhibitory Peptides Attenuates Fibrosis and Inducibility of Atrial Fibrillation in a Canine Heart Failure Model

Introduction: Endothelial dysfunction, a hallmark of heart failure (HF), is closely associated with atrial fibrillation (AF). However, the precise role of endothelial dysfunction in creating an atrial arrhythmogenic substrate is unknown. Endothelin-1 (ET-1) and its downstream Gα q signaling are significantly upregulated in the atria of patients with HF. We therefore hypothesized that ET-1-Gα q signaling contributes to adverse structural remodeling in the atria in the setting of HF. Hypothesis: Inhibition of atrial ET-1-Gα q signaling with Gα q inhibitory peptides (Gα q -ct) will attenuate the development of atrial fibrosis and AF inducibility in a HF model. Methods: Plasmids expressing Gα q -ct were injected and electroporated in the left atria of 4 dogs. LacZ or scrambled plasmids were used in 8 control dogs. HF was induced by ventricular tachypacing (VTP) at 240 bpm for 3 weeks. At terminal EP study, left atrial conduction vectors were recorded with high-density mapping and AF inducibility assessed. Left atrial fibrosis was quantified by Masson Trichrome. Results: All animals developed clinical HF (prolonged capillary refill time, ascites, reduced activity level) and LV systolic dysfunction by echocardiogram (LVEF 17.5±8.3% in Gα q -ct, 13.7±3.1% in controls, p=0.55). Conduction inhomogeneity was reduced in Gα q -ct animals (example of posterior left atrium recordings in Fig. A). AF was less inducible in Gα q -ct than control animals (4.8% of pacing attempts Vs 17.8%, p&lt;0.001, Fig. B) and AF episodes were shorter (5.6±0.9 sec Vs 63.8±11.9 sec). Left atrial fibrosis was significantly attenuated in Gα q -ct animals Vs controls (Fig. C). Conclusions: Gα q signaling contributes to atrial fibrosis and subsequent AF susceptibility in VTP-induced HF, thereby highlighting an important role for ET-1 signaling in HF-related atrial remodeling. Future optimization of gene therapy targeting ET-1 signaling may lead to novel, mechanism-guided treatments for AF in the context of HF.

Atrial fibrillation in embolic stroke of undetermined source: role of advanced imaging of left atrial function.

Atrial fibrillation (AF) is detected in over 30% of patients following an embolic stroke of undetermined source (ESUS) when monitored with an implantable loop recorder (ILR). Identifying AF in ESUS survivors has significant therapeutic implications, and AF risk is essential to guide screening with long-term monitoring. The present study aimed to establish the role of left atrial (LA) function in subsequent AF identification and develop a risk model for AF in ESUS. We conducted a single-centre retrospective case-control study including all patients with ESUS referred to our institution for ILR implantation from December 2009 to September 2019. We recorded clinical variables at baseline and analysed transthoracic echocardiograms in sinus rhythm. Univariate and multivariable analyses were performed to inform variables associated with AF. Lasso regression analysis was used to develop a risk prediction model for AF. The risk model was internally validated using bootstrapping. Three hundred and twenty-three patients with ESUS underwent ILR implantation. In the ESUS population, 293 had a stroke, whereas 30 had suffered a transient ischaemic attack as adjudicated by a senior stroke physician. Atrial fibrillation of any duration was detected in 47.1%. The mean follow-up was 710 days. Following lasso regression with backwards elimination, we combined increasing lateral PA (the time interval from the beginning of the P wave on the surface electrocardiogram to the beginning of the A' wave on pulsed wave tissue Doppler of the lateral mitral annulus) [odds ratio (OR) 1.011], increasing Age (OR 1.035), higher Diastolic blood pressure (OR 1.027), and abnormal LA reservoir Strain (OR 0.973) into a new PADS score. The probability of identifying AF can be estimated using the formula. Model discrimination was good [area under the curve (AUC) 0.72]. The PADS score was internally validated using bootstrapping with 1000 samples of 150 patients showing consistent results with an AUC of 0.73. The novel PADS score can identify the risk of AF on prolonged monitoring with ILR following ESUS and should be considered a dedicated risk stratification tool for decision-making regarding the screening strategy for AF in stroke.

PO-03-074 INITIAL HEART RATE SCORE IS PREDICTOR FOR OCCURRENCE OF NEW ATRIAL FIBRILLATION INDEPENDENT OF WELL-KNOWN RISK FACTORS AND RELATES TO RIGHT ATRIAL PACING RATE IN PACEMAKER PATIENTS

Heart Rate Score (HRSc), the percent of right atrial (RA) beats in the largest paced or sensed 10-bpm histogram bin, predicts survival in ICD and CRT-D patients without atrial fibrillation (AF). For pacemaker (PM) patients, although age, gender and RA and right ventricular pacing percent (% RA and RV pacing) have been related to AF, the relationship of HRSc to subsequent AF is unknown. To evaluate the relationship between initial post implantation HRSc and incidence of newly developed AF, and well-known predictors for AF in PM patients. Patients with dual-chamber, atrial tracking PMs, implanted 2013-2017, who had ALTITIUDE remote monitoring data available, were included. HRSc was determined from histogram data during the first 3 months post-implant. Only patients with ≥600,000 beats of histogram data collected at baseline were included. Patients with single-chamber or biventricular PMs were excluded. Patients were excluded if they had AF, defined as atrial high rate episodes >5 minutes or >1% of RA beats >170 bpm during the initial 3-months post-implant. AF after the baseline period was evaluated by the definition: >1% of atrial beats >170 bpm. Sinus node disease (SND) was defined as needed for RA pacing ≥ 40% and atrio-ventricular block (AVB) as needed for right ventricular pacing ≥ 20% during the baseline period. Of the total population (N=34,543), 15,252 patients had device-determined SND and 16,190 patients had AVB. Utilizing multivariable analysis, the initial HRSc (HR: 1.07, 95% CI: 1.05-1.09; P<0.0001) independently predicted subsequent AF after adjusting for age, gender, % RV pacing and rate-response programming. Patients with initial HRSc≥70% were older, and had higher % RA pacing, lower % RV pacing and were more likely programmed with rate-response vs subjects with initial HRSc<70%. There was a direct, and significant, increase in new-onset AF with each 20% increment in HRSc and/or % RA pacing (both P<0.001, Figure) during median of 2.8 (1.0-4.0) years follow-up. The %RA pacing and initial HRSc were strongly correlated (Pearson correlation coefficient=0.9). % RV pacing did not predict AF. Both SND patients and AVB patients with initial HRSc≥70% had a significantly increased risk of AF (log-rank P <0.001) compared to patients with HRSc<70%. Initial HRSc, strongly related to percent RA pacing, predicts subsequent AF independent of well-known risk factors in both device-determined SND and AVB.

Utility of an Artificial Intelligence Enabled Electrocardiogram for Risk Assessment in Liver Transplant Candidates.

Post-operative cardiac complications occur infrequently but contribute to mortality after liver transplantation (LT). Artificial intelligence-based algorithms based on electrocardiogram (AI-ECG) are attractive for use during pre-operative evaluation to screen for risk of post-operative cardiac complications, but their use for this purpose is unknown. The aim of this study was to evaluate the performance of an AI-ECG algorithm in predicting cardiac factors such as asymptomatic left ventricular systolic dysfunction or potential for developing post-operative atrial fibrillation (AF) in cohorts of patients with end-stage liver disease either undergoing evaluation for transplant or receiving a liver transplant. A retrospective study was performed in two consecutive adult cohorts of patients who were either evaluated for LT or underwent LT at a single center between 2017 and 2019. ECG were analyzed using an AI-ECG trained to recognize patterns from a standard 12-lead ECG which could identify the presence of left ventricular systolic dysfunction (LVEF < 50%) or subsequent atrial fibrillation. The performance of AI-ECG in patients undergoing LT evaluation is similar to that in a general population but was lower in the presence of prolonged QTc. AI-ECG analysis on ECG in sinus rhythm had an AUROC of 0.69 for prediction of de novo post-transplant AF. Although post-transplant cardiac dysfunction occurred in only 2.3% of patients in the study cohorts, AI-ECG had an AUROC of 0.69 for prediction of subsequent low left ventricular ejection fraction. A positive screen for low EF or AF on AI-ECG can alert to risk of post-operative cardiac dysfunction or predict new onset atrial fibrillation after LT. The use of an AI-ECG can be a useful adjunct in persons undergoing transplant evaluation that can be readily implemented in clinical practice.

TRIM21 deficiency protects against atrial inflammation and remodeling post myocardial infarction by attenuating oxidative stress

Atrial remodeling is a major contributor to the onset of atrial fibrillation (AF) after myocardial infarction (MI). Tripartite motif-containing protein 21 (TRIM21), an E3 ubiquitin protein ligase, is associated with pathological cardiac remodeling and dysfunction. However, the role of TRIM21 in postmyocardial infarction atrial remodeling and subsequent AF remains unclear. This study investigated the role of TRIM21 in post myocardial infarction atrial remodeling using TRIM21 knockout mice and explored the underlying mechanisms by overexpressing TRIM21 in HL-1 atrial myocytes using a lentiviral vector. The expression of TRIM21 in the left atrium of the mouse MI model was significantly elevated. TRIM21 deficiency alleviated MI-induced atrial oxidative damage, Cx43 downregulation, atrial fibrosis and enlargement, and abnormalities in electrocardiogram parameters (prolongation of the P-wave and PR interval). TRIM21 overexpression in atrial myocyte HL-1 cells further enhanced oxidative damage and Cx43 downregulation, whereas these effects were reversed by the reactive oxygen species scavenger N-acetylcysteine. The findings suggest that TRIM21 likely induces Nox2 expression mechanistically by activating the NF-κB pathway, which in turn leads to myocardial oxidative damage, inflammation, and atrial remodeling.

Sex-based comparisons of clinical characteristics and outcomes of patients with embolic stroke of undetermined source with implantable loop recorders

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Embolic strokes of undetermined source (ESUS) constitute a significant proportion of all ischemic strokes, but sex-based comparisons of clinical characteristics and outcomes of ESUS patients have not been well explored. As such, we aimed to examine how sex influences outcomes of ESUS patients. Methods Retrospective cohort study performed on consecutive ESUS patients with an implanted ILR between December 2013 to September 2021. We obtained information on the patients’ characteristics, treatments, and outcomes from the electronic medical records. Cox regression was used to investigate whether sex was independently associated with outcomes. Results There were 176 patients included in this study. The mean duration of follow-up was 1254 ± 724 days. Mean age was 60.8 ± 12.0 and 47 (26.7%) of patients were female. On univariable Cox regression analysis for subsequent atrial fibrillation (AF) on implantable loop recorder (ILR), patients with subsequent AF on ILR were more likely to be female (HR 2.19, 95% CI 1.04–4.63, p = 0.040), older (HR 1.07, 95% CI 1.03–1.12, p = 0.001), have a lower glomerular filtration rate (eGFR) (HR 0.98, 95% CI 0.97– 0.99, p = 0.004), and have previous percutaneous coronary intervention (PCI) (HR 2.60, 95% CI 1.05–6.46, p = 0.039). On multivariable Cox regression, after adjustment for age, eGFR and previous PCI status, female sex remained independently associated with the development of subsequent AF on ILR. Female sex was not associated with other outcomes including mortality, subsequent acute myocardial infarction, stroke/transient ischemic attack and heart failure. Conclusions In this cohort of ESUS patients with ILR implantation, female sex was independently associated with a higher risk of development of AF on ILR. However, female sex was not a predictor of mortality, subsequent acute myocardial infarction, stroke/transient ischemic attack and heart failure.

Epidemiology and modifiable risk factors for atrial fibrillation.

The global prevalence of atrial fibrillation (AF) has increased substantially over the past three decades and is currently approximately 60 million cases. Incident AF and its clinical consequences are largely the result of risk factors that can be modified by lifestyle changes. In this Review, we provide evidence that the lifetime risk of AF is modified not only by sex and race but also through the clinical risk factor and comorbidity burden of individual patients. We begin by summarizing the epidemiology of AF, focusing on non-modifiable and modifiable risk factors, as well as targets and strategies for theprimary prevention of AF. Furthermore, we evaluate the role of modifiable risk factors in the secondary prevention of AF as well as the potential effects of risk factor interventions on the frequency and severity of subsequent AF episodes. We end the Review by proposing strategies that require evaluation as well as global policy changes that are needed for the prevention of incident AF and the management of recurrent episodes in patients already affected by AF.

Adipose Triglyceride Lipase Deficiency Aggravates Angiotensin II–Induced Atrial Fibrillation by Reducing Peroxisome Proliferator–Activated Receptor α Activation in Mice

Atrial fibrillation (AF) is a main risk factor for cerebrovascular diseases but lacks precision therapy. Adipose triglyceride lipase (ATGL) is a key enzyme involved in the intracellular degradation of triacylglycerol and plays an important role in lipid and energy metabolism. However, the role of ATGL in the regulation of AF remains unclear. In this study, AF was induced by infusion of angiotensin II (Ang II, 2000 ng/kg/min) for 3 weeks in male ATGL knockout (KO) mice and age-matched C57BL/6 wild-type mice. The atrial volume was measured by echocardiography. Atrial fibrosis, inflammatory cells, and superoxide production were detected by histologic examinations. The results showed that ATGL expression was significantly downregulated in the atrial tissue of the Ang II–infused mice. Moreover, Ang II–induced increase in the inducibility and duration of AF, atrial dilation, fibrosis, inflammation, and oxidative stress in wild-type mice were markedly accelerated in ATGL KO mice; however, these effects were dramatically reversed in the ATGL KO mice administered with peroxisome proliferator–activated receptor (PPAR)-α agonist clofibric acid. Mechanistically, Ang II downregulated ATGL expression and inhibited PPAR-α activity, activated multiple signaling pathways (inhibiting kappa B kinase α/β-nuclear factor-κB, nicotinamide adenine dinucleotide phosphate oxidase, and transforming growth factor-β1/SMAD2/3) and reducing Kv1.5, Cx40, and Cx43 expression, thereby contributing to atrial structural and electrical remodeling and subsequent AF. In summary, our results indicate that ATGL KO enhances AF inducibility, possibly through inhibiting PPAR-α activation and suggest that activating ATGL might be a new therapeutic option for treating hypertensive AF.

Comparison of advanced generation cryoballoon ablation and ablation index-guided pulmonary vein isolation with non-pulmonary vein trigger induction test and additional ablation in paroxysmal atrial fibrillation.

An ablation index (AI)-guided pulmonary vein isolation (PVI) or 2nd generation cryoballoon (CB)-PVI has been shown to reduce the atrial fibrillation (AF) burden by 99% despite the absence of ablation of non-pulmonary vein (PV) triggers in patients with paroxysmal AF. The purpose of this study was to investigate the effects of PVI alone strategy using 2nd generation CB compared with AI-guided PVI with an additional induction test and subsequent AF trigger ablation. We investigated 223 patients with symptomatic paroxysmal AF who underwent an initial PVI between August 2018 and August 2020. The study patients were divided into 2 groups: CB-PVI without an induction test (CB-PVI alone group, n = 82) and AI-guided PVI with an induction test and subsequent additional ablation of non-PV triggers (AI-PVI plus group, n = 141). In the AI-PVI plus group, a total of 62 non-PV triggers were induced in 38 patients, and non-PV triggers in 22 patients were completely ablated. The procedure time and left atrium dwell time were significantly shorter in the CB-PVI alone group than AI-PVI plus group. There were no significant differences in the incidence of procedural complications between the 2 groups (P = 0.650). The AF free survival rate in the CB-PVI alone group and AI-PVI plus group was 80% vs. 80% at 24months (P = 0.969). An PVI alone strategy using advanced generation CB did not differ in the clinical outcomes compared with an AI-guided PVI strategy with an induction test and subsequent ablation of non-PV triggers in the patients with paroxysmal AF.