Frequent Premature Atrial Complexes Research Articles

Frequent Premature Atrial Contractions Lead to Adverse Atrial Remodeling and Atrial Fibrillation in a Swine Model.

Frequent premature atrial complexes (PACs) are associated with future incident atrial fibrillation (AF), but whether PACs contribute to development of AF through adverse atrial remodeling has not been studied. This study aimed to explore the effect of frequent PACs from different sites on atrial remodeling in a swine model. Forty swine underwent baseline electrophysiologic studies and echocardiography followed by pacemaker implantations and paced PACs (50% burden) at 250-ms coupling intervals for 16 weeks in 4 groups: (1) lateral left atrium (LA) PACs by the coronary sinus (Lat-PAC; n=10), (2) interatrial septal PACs (Sep-PAC; n=10), (3) regular LA pacing at 130 beats/min (Reg-130; n=10), and (4) controls without PACs (n=10). At the final study, repeat studies were performed, followed by tissue histology and molecular analyses focusing on fibrotic pathways. Lat-PACs were associated with a longer P-wave duration (93.0±9.0 versus 74.2±8.2 and 58.8±7.6 ms; P<0.001) and greater echocardiographic mechanical dyssynchrony (57.5±11.6 versus 35.7±13.0 and 24.4±11.1 ms; P<0.001) compared with Sep-PACs and controls, respectively. After 16 weeks, Lat-PACs led to slower LA conduction velocity (1.1±0.2 versus 1.3±0.2 [Sep-PAC] versus 1.3±0.1 [Reg-130] versus 1.5±0.2 [controls] m/s; P<0.001) without significant change in atrial ERP. The Lat-PAC group had a significantly increased percentage of LA fibrosis and upregulated levels of extracellular matrix proteins (lysyl oxidase and collagen 1 and 8), as well as TGF-β1 (transforming growth factor-β1) signaling proteins (latent and monomer TGF-β1 and phosphorylation/total ratio of SMAD2/3; P<0.05). The Lat-PAC group had the longest inducible AF duration (terminal to baseline: 131 [interquartile range 30, 192] seconds versus 16 [6, 26] seconds [Sep-PAC] versus 22 [11, 64] seconds [Reg-130] versus -1 [-16, 7] seconds [controls]; P<0.001). In this swine model, frequent PACs resulted in adverse atrial structural remodeling with a heightened propensity to AF. PACs originating from the lateral LA produced greater atrial remodeling and longer induced AF duration than the septal-origin PACs. These data provide evidence that frequent PACs can cause adverse atrial remodeling as well as AF, and that the location of ectopic PACs may be clinically meaningful.

PO-01-161 PIRFENIDONE MITIGATES THE DEVELOPMENT OF ARRHYTHMOGENIC ATRIAL FIBROSIS DUE TO PREMATURE ATRIAL COMPLEXES IN A SWINE MODEL

Atrial fibrosis is one of the major pathophysiologic mechanisms underlying the progression of atrial arrhythmias. We previously demonstrated in a swine model that frequent premature atrial complexes (PACs) promote atrial fibrillation (AF) via atrial fibrosis and slow conduction. Whether such fibrosis can be reversed or prevented is unknown. To evaluate the effect of (1) PAC eradication and (2) the antifibrotic drug pirfenidone (PFD) on atrial fibrosis in a swine model of frequent, dyssynchronous PACs. Thirty-five swine were exposed to 50% paced PACs from the lateral left atrium (LA) via the coronary sinus for 16 weeks in 4 groups: (1) controls without PACs (CTRL, n=10); (2) PAC group (PAC; n=10); 3) PACs followed by additional 6 weeks of PAC cessation (Rec-PAC, n=10); and (4) PACs treated with oral PFD (801mg 2 times per day) (PFD-PAC; n=5). Detailed EP study and echocardiography were performed at baseline and prior to sacrifice followed by blinded histological quantification of LA fibrosis. In the PAC group, peak atrial strain declined significantly at 16 weeks compared to CTRL. Compared to the PAC group, both the Rec-PAC and PFD-PAC groups had a less significant decline in peak atrial strain (terminal - baseline: PAC -17.7±3.3% vs. Rec-PAC -8.3±3.2% vs. PFD-PAC -11.5±3.0% vs. CTRL -0.7±4.2%; p<0.001). Conduction velocity (CV) was significantly decreased in PAC and Rec-PAC, but this decrease was attenuated in the PFD-PAC group (PAC CV 1.1±0.2m/s vs. Rec-PAC 1.2±0.1 m/s vs. PFD-PAC 1.3±0.1m/s vs. CTRL 1.5±0.2m/s; p<0.001). Posterior wall LA fibrosis was significantly increased in the PAC group, with no significant change after 6 weeks of recovery without PACs. However, the PFD-PAC group showed significantly lower fibrosis than either the PAC or Rec-PAC groups (Figure, Panel A). The PFD-PAC group also had less AF inducibility compared to the PAC and Rec-PAC groups (Panel B). In a swine model, frequent PACs produce atrial fibrosis and arrhythmogenic AF substrate. This fibrotic substrate did not regress after 6 weeks without PACs. However, treatment with PFD significantly attenuated the development of atrial fibrosis and AF inducibility. These findings suggest: (1) early management may be important for preventing ectopy-induced adverse atrial remodeling, and (2) pharmacological therapy targeted at the fibrotic substrate may play an important, novel role in the prevention of atrial remodeling and the substrate for developing AF.

PO-455617-18 SHORT COUPLED PREMATURE ATRIAL COMPLEXES LEAD TO ADVERSE ATRIAL REMODELING AND ATRIAL FIBRILLATION IN A SWINE MODEL

Frequent premature atrial complexes (PACs) are associated with left atrial (LA) myopathy and atrial fibrillation (AF), however, the effect of coupling interval and irregularity on the ensuing atrial myopathy has not been tested. To explore the impact of coupling interval and regularity of atrial ectopics on the development of atrial remodeling and AF in a swine model. Thirty-five swine underwent baseline electrophysiologic study followed by pacemaker implantation and pacing from the lateral LA via the coronary sinus for 16 weeks in 4 groups: 1) controls without PACs (CTRL, n=10); 2) 50% paced PACs at a short coupling interval (CI) of 250ms (Short-PAC, n=10); 3) 50% PACs at a long CI of 400ms (Long-PAC, n=5); and 4) regular pacing at a faster mean atrial rate (130 beats/min) than during PACs (Reg-130, n=10). At the terminal study, a repeat electrophysiologic study was performed followed by sacrifice and histologic analysis. Structural changes: The Short-PAC group had the greater degree of LA dilation (terminal - baseline: Short-PAC 5.9±1.2cm2 vs. Long-PAC 3.9±0.5cm2 vs. Reg-130 3.0±1.0cm2 vs. CTRL 0.9±0.3cm2, p<0.001) and decrease in peak LA strain (terminal - baseline: Short-PAC -17.3±3.2% vs. Long-PAC -12.7±2.9% vs. Reg-130 -8.2±2.9% vs. CTRL -0.7±4.2%, p<0.001). Electrophysiologic changes: The Short-PAC group had slower LA conduction velocity than the Reg-130 and CTRL groups (Short-PAC 1.1±0.2m/s vs. Long-PAC 1.2±0.1m/s vs. Reg-130 1.3±0.1m/s vs. CTRL 1.5±0.2m/s, p<0.001); atrial effective refractory period (ERP) was only decreased in the Reg-130 group (terminal - baseline: Short-PAC -4.0±23.6ms vs. Long-PAC -8.7±17.9ms vs. Reg-130 -23.7±14.3ms vs. CTRL -3.2±23.7ms, p=0.09). Fibrosis: percent LA fibrosis was highest in the Short-PAC group followed by Long-PAC, Reg-130, and then CTRL groups (Figure, Panel A). AF induction: The Short-PAC group had the longest duration of induced AF (Panel B). In a swine model, frequent PACs can cause structural and electrical atrial remodeling with a heightened propensity for AF. PACs led to slow conduction and fibrosis without change in atrial ERP, suggesting a process distinct from tachy-pacing induced atrial remodeling. Moreover, PACs with short CIs resulted in a greater degree of LA remodeling and induced AF duration compared to PACs with long CIs. These findings suggest that frequent, short coupled PACs pose the highest risk for developing atrial remodeling and AF.

PO-455617-17 PIRFENIDONE MITIGATES THE DEVELOPMENT OF ARRHYTHMOGENIC ATRIAL FIBROSIS DUE TO PREMATURE ATRIAL COMPLEXES IN A SWINE MODEL

Atrial fibrosis is one of the major pathophysiologic mechanisms underlying the progression of atrial arrhythmias. We previously demonstrated in a swine model that frequent premature atrial complexes (PACs) promote atrial fibrillation (AF) via atrial fibrosis and slow conduction. Whether such fibrosis can be reversed or prevented is unknown. To evaluate the effect of (1) PAC eradication and (2) the antifibrotic drug pirfenidone (PFD) on atrial fibrosis in a swine model of frequent, dyssynchronous PACs. Thirty-five swine were exposed to 50% paced PACs from the lateral left atrium (LA) via the coronary sinus for 16 weeks in 4 groups: (1) controls without PACs (CTRL, n=10); (2) PAC group (PAC; n=10); 3) PACs followed by additional 6 weeks of PAC cessation (Rec-PAC, n=10); and (4) PACs treated with oral PFD (801mg 2 times per day) (PFD-PAC; n=5). Detailed EP study and echocardiography were performed at baseline and prior to sacrifice followed by blinded histological quantification of LA fibrosis. In the PAC group, peak atrial strain declined significantly at 16 weeks compared to CTRL. Compared to the PAC group, both the Rec-PAC and PFD-PAC groups had a less significant decline in peak atrial strain (terminal - baseline: PAC -17.7±3.3% vs. Rec-PAC -8.3±3.2% vs. PFD-PAC -11.5±3.0% vs. CTRL -0.7±4.2%; p<0.001). Conduction velocity (CV) was significantly decreased in PAC and Rec-PAC, but this decrease was attenuated in the PFD-PAC group (PAC CV 1.1±0.2m/s vs. Rec-PAC 1.2±0.1 m/s vs. PFD-PAC 1.3±0.1m/s vs. CTRL 1.5±0.2m/s; p<0.001). Posterior wall LA fibrosis was significantly increased in the PAC group, with no significant change after 6 weeks of recovery without PACs. However, the PFD-PAC group showed significantly lower fibrosis than either the PAC or Rec-PAC groups (Figure, Panel A). The PFD-PAC group also had less AF inducibility compared to the PAC and Rec-PAC groups (Panel B). In a swine model, frequent PACs produce atrial fibrosis and arrhythmogenic AF substrate. This fibrotic substrate did not regress after 6 weeks without PACs. However, treatment with PFD significantly attenuated the development of atrial fibrosis and AF inducibility. These findings suggest: (1) early management may be important for preventing ectopy-induced adverse atrial remodeling, and (2) pharmacological therapy targeted at the fibrotic substrate may play an important, novel role in the prevention of atrial remodeling and the substrate for developing AF.

PO-01-001 SHORT COUPLED PREMATURE ATRIAL COMPLEXES LEAD TO ADVERSE ATRIAL REMODELING AND ATRIAL FIBRILLATION IN A SWINE MODEL

Frequent premature atrial complexes (PACs) are associated with left atrial (LA) myopathy and atrial fibrillation (AF), however, the effect of coupling interval and irregularity on the ensuing atrial myopathy has not been tested. To explore the impact of coupling interval and regularity of atrial ectopics on the development of atrial remodeling and AF in a swine model. Thirty-five swine underwent baseline electrophysiologic study followed by pacemaker implantation and pacing from the lateral LA via the coronary sinus for 16 weeks in 4 groups: 1) controls without PACs (CTRL, n=10); 2) 50% paced PACs at a short coupling interval (CI) of 250ms (Short-PAC, n=10); 3) 50% PACs at a long CI of 400ms (Long-PAC, n=5); and 4) regular pacing at a faster mean atrial rate (130 beats/min) than during PACs (Reg-130, n=10). At the terminal study, a repeat electrophysiologic study was performed followed by sacrifice and histologic analysis. Structural changes: The Short-PAC group had the greater degree of LA dilation (terminal - baseline: Short-PAC 5.9±1.2cm2 vs. Long-PAC 3.9±0.5cm2 vs. Reg-130 3.0±1.0cm2 vs. CTRL 0.9±0.3cm2, p<0.001) and decrease in peak LA strain (terminal - baseline: Short-PAC -17.3±3.2% vs. Long-PAC -12.7±2.9% vs. Reg-130 -8.2±2.9% vs. CTRL -0.7±4.2%, p<0.001). Electrophysiologic changes: The Short-PAC group had slower LA conduction velocity than the Reg-130 and CTRL groups (Short-PAC 1.1±0.2m/s vs. Long-PAC 1.2±0.1m/s vs. Reg-130 1.3±0.1m/s vs. CTRL 1.5±0.2m/s, p<0.001); atrial effective refractory period (ERP) was only decreased in the Reg-130 group (terminal - baseline: Short-PAC -4.0±23.6ms vs. Long-PAC -8.7±17.9ms vs. Reg-130 -23.7±14.3ms vs. CTRL -3.2±23.7ms, p=0.09). Fibrosis: percent LA fibrosis was highest in the Short-PAC group followed by Long-PAC, Reg-130, and then CTRL groups (Figure, Panel A). AF induction: The Short-PAC group had the longest duration of induced AF (Panel B). In a swine model, frequent PACs can cause structural and electrical atrial remodeling with a heightened propensity for AF. PACs led to slow conduction and fibrosis without change in atrial ERP, suggesting a process distinct from tachy-pacing induced atrial remodeling. Moreover, PACs with short CIs resulted in a greater degree of LA remodeling and induced AF duration compared to PACs with long CIs. These findings suggest that frequent, short coupled PACs pose the highest risk for developing atrial remodeling and AF.

Electrocardiographic Waveform Abnormalities in Patients With Structural Heart Disease

Scenario: This 12-lead electrocardiogram (ECG) was obtained in a 72-year-old man arriving in the emergency department with shortness of breath and dizziness. Prior medical history includes myocardial infarction (MI), heart failure (HF), chronic obstructive pulmonary disease (COPD), diabetes (type 2), and paroxysmal atrial fibrillation. Current prescribed medications include a β-blocker, aspirin, angiotensin-converting enzyme inhibitor, furosemide, and diltiazem. His blood pressure was 98/50 mm Hg, respiratory rate 24/min, and oxygen saturation as measured by pulse oximetry (Spo2) was 92% on 3 L of oxygen. He was most comfortable sitting up with his arms on the bedside table, and said he felt better after 40 mg of furosemide was administered intravenously.Sinus rhythm with premature atrial complexes (PACs), possible right and left atrial enlargement, prior inferior wall MI (q waves in leads III and aVF), incomplete left intraventricular conduction defect (fQRS waves), left ventricular hypertrophy, and ST-segment and T-wave abnormalities may suggest anterolateral ischemia.Although the underlying rhythm is irregular, suggesting atrial fibrillation, P waves are visible before every QRS complex; thus, this is sinus rhythm with frequent PACs. PACs are not uncommon in patients with structural heart disease and COPD, like this one. The pause after the PACs is a normal physiologic response and represents a compensatory pause associated with PACs. The ECG criterion for right atrial enlargement is a P-wave amplitude greater than 2.5 mm in leads II, III, and aVF (so-called P pulmonale) and can be seen with COPD. Left atrial enlargement is due to pressure or volume overload of the left atrium and can be assessed in V1 (biphasic P waves with negative terminal portion >40 ms long and >1 mm deep). Biatrial enlargement is consistent with this patient’s medical history (MI, HF, and left ventricular hypertrophy); however, ECG is not the reference standard method, so the diagnosis should be confirmed by echocardiography. The T-wave inversion and ST-segment depression most likely represent a “strain” pattern seen with left ventricular hypertrophy, but acute myocardial ischemia should be ruled out given the patient’s prior MI.Immediate management includes addressing the acute respiratory distress and low blood pressure, with HF exacerbation a likely source. This patient’s symptoms were somewhat relieved after the intravenous furosemide, which supports this diagnosis. Checking a venous blood sample for brain natriuretic peptide (BNP) to assess for HF, troponin to rule out myocardial ischemia, and electrolyte levels would help. A chest radiograph would be useful, as might arterial blood gas analysis, given his elevated rate of breathing and the 92% Spo2 with 3 L of oxygen. Findings on physical examination, especially lung and heart sounds, peripheral edema, and daily weight should be evaluated. Ultimately, this patient’s BNP level was 3400 ng/mL, which corroborates HF, and his troponin was negative for myocardial ischemia. He was discharged home 3 days later.

Presentation and Prognosis of Excessive Asymptomatic Atrial Ectopy in Children and Adolescents With Structurally and Functionally Normal Hearts

Excessive premature atrial complexes (PACs) in pediatric patients with a structurally normal heart are presumed to be benign and self-resolving, but no studies have confirmed this. Adults with excessive PACs, however, are at increased risk for future sustained atrial arrhythmias and cardiovascular morbidity and mortality. Therefore, we sought to evaluate the clinical course of frequent PACs in asymptomatic children. Patients < 21 years old with numerous asymptomatic PACs (>50/24 hours) were retrospectively selected over a 10-year period. Demographics, clinical characteristics, and results of cardiovascular testing were tabulated. Two groups were defined: those with a significant (>20%) reduction in burden of atrial ectopy versus those with an insignificant (<20%) reduction or increase. Of 6,902 patients, 343 patients (5%) met criteria. Initial median age was 8.3 (interquartile range [IQR] 4.1 to 14) years with comparable male:female ratio. Follow-up Holters were performed on 188 patients (54.8%) at a median interval of 2.2 (IQR 1.3 to 3.6) years. Overall, there was a significant decrease in atrial ectopy burden from 4.2% (IQR 1.9 to 6.5) down to 0.5% (IQR 0.01 to 2.3), with 166 patients (88.3%), demonstrating a decrease of over 20%. Five percent had a small increase, and 6% had an insignificant decrease. None developed cardiac symptoms or sustained supraventricular tachydysrhythmia. Male gender, athletic participation, and discontinuation of stimulant medications were the chief predictors for a reduction of PAC burden on follow-up. Atrial triplets at presentation were associated with a 5.4% increase. In conclusion, this study confirms that excessive asymptomatic childhood PACs with structurally normal hearts are rare and short-term to medium-term prognosis is benign.

Abstract 14295: Asymptomatic Frequent Atrial Ectopy in Healthy Children and Adolescents

Introduction: Premature atrial complexes (PACs) in pediatric patients with a structurally normal heart are usually presumed to be benign and self-resolving. On the contrary, adults with frequent PACs are at increased risk of multiple cardiovascular conditions. This study aims to evaluate a group of asymptomatic pediatric subjects with frequent PACs over time. Hypothesis: We hypothesized that, while most pediatric patients with frequent APCs have a benign prognosis there may be a subset that could progress to supraventricular arrhythmias Methods: Records for 343 pediatric patients (1-21 yrs) with asymptomatic frequent premature atrial complexes (&gt;50/24 hours) were selected from 6902 pediatric patients that underwent Holters over a 10 year period. Demographics, pertinent clinical characteristics and results of cardiac investigations were tabulated. Comparisons were made between Holter results at presentation and follow-up. Patients were classified into two groups on follow-up, those with a significant (&gt;20%) reduction in burden of atrial ectopy versus those with an insignificant (&lt;20%) reduction or increase in burden of atrial ectopy. Results: The median age at initial Holter was 8.26 (1.3-20.9) years with a comparable male to female ratio. An irregular heart rate was the most common reason for a Holter. The most common preexisting medical condition was attention deficit disorder, followed by asthma. Follow-up Holters were performed on 188(54.8%) patients at a median of 2.2 (0.5-8) yrs after the first Holter. Overall there was a significant decrease in atrial ectopy burden on repeat Holter examinations; median 3.6% (0.03-18.7) to 0.5% (0-19) with 166 (88.3%) patients demonstrating a decrease in atrial ectopy by over 20% of baseline. Ten (5.3%) patients had an increase in the ectopy burden over time and 12(6.3%) had an insignificant change. Non sustained supraventricular tachycardia was noted in three patients on the initial Holter but none on subsequent evaluations. Multivariate analysis identified a higher initial burden of PACs as a strong independent predictor for reduction in burden of ectopy with time (p&lt;0.005). Conclusions: Asymptomatic childhood PACs in the setting of a structurally normal heart are rare and tend to resolve with time.

PO-653-04 FREQUENT DYSSYNCHRONOUS PREMATURE ATRIAL CONTRACTIONS LEAD TO ADVERSE REMODELING AND ATRIAL FIBRILLATION IN A SWINE MODEL

Frequent premature atrial complexes (PACs) are associated with future incident atrial fibrillation (AF), but whether PACs contribute to the development of AF through adverse atrial remodeling has not been studied.

Abstract 12116: Sex Differences in Arrhythmia Prevalence in a Large Patient Cohort Examined With Mobile Cardiac Telemetry

Introduction: The frequency of clinically relevant arrhythmia on long-term ambulatory ECG recordings is not sufficiently well described. We aimed to address this in a large patient cohort monitored with mobile cardiac telemetry. Methods: All patients 18-100 years who were monitored in the USA in 2017 (n=27.203, 58% female) with the PocketECG device (MediLynx), which registers and transmits a full-disclosure ECG for ≤30 days with beat-to-beat analysis, were included. Frequent premature ventricular complexes (PVCs) and frequent premature atrial complexes (PACs) were defined as ≥200 PVCs or ≥500 PACs in any recording day. Supraventricular tachycardia (SVT) episodes were defined as both any SVT &gt;3 beats, and SVT ≥30 seconds. AV-blocks II and III were not differentiated. Results: In the 18-40-year age group the overall prevalence of any arrhythmia was low (Figure 1 a-f). Frequent PACs, atrial fibrillation, AV-blocks and ventricular arrhythmias were more common in men than women (all p&lt;0.0001), and SVTs, both &gt;3 beats and &gt;30 seconds, were more common in women (p&lt;0.001 and p&lt;0.004, respectively). The overall prevalence of any VT event was 22.9% in women and 40.8% in men (p&lt;0.0001) and the mean age at onset of VT was lower in women (71.9 vs 72.6 years, 95%CI for difference (-1.3; -0.3). Conclusions: Most arrhythmias are more prevalent among men of all ages, but SVTs are more prevalent among women. VT events are common in a patient population, and the age at onset of ventricular tachycardia is lower among women.

Targeting non-pulmonary vein triggers in persistent atrial fibrillation: results from a prospective, multicentre, observational registry.

We evaluated the efficacy of an ablation strategy empirically targeting pulmonary veins (PVs) and posterior wall (PW) and the prevalence and clinical impact of extrapulmonary trigger inducibility and ablation in a large cohort of patients with persistent atrial fibrillation (PerAF). A total of 1803 PerAF patients were prospectively enrolled. All patients underwent pulmonary vein antrum isolation (PVAI) extended to the entire PW. A standardized protocol was performed to confirm persistent PVAI and elicit any triggers originating from non-PV sites. All non-PV triggers initiating sustained atrial tachyarrhythmias were ablated. Ablation of non-PV sites triggering non-sustained runs (<30 s) of atrial tachyarrhythmias or promoting frequent premature atrial complexes (≥10/min) was left to operator's discretion. Overall, 1319 (73.2%) patients had documented triggers from non-PV areas. After 17.4 ± 8.5 months of follow-up, the cumulative freedom from atrial tachyarrhythmias among patients without inducible non-PV triggers (n = 484) was 70.2%. Patients with ablation of induced non-PV triggers had a significantly higher arrhythmia control than those whose triggers were not ablated (67.9% vs. 39.4%, respectively; P < 0.001). After adjusting for clinically relevant variables, patients in whom non-PV triggers were documented but not ablated had an increased risk of arrhythmia relapse (hazard ratio: 2.39; 95% confidence interval: 2.01-2.83; P < 0.001). Pulmonary vein antrum isolation extended to the entire PW might provide acceptable long-term arrhythmia-free survival in PerAF patients without inducible non-PV triggers. In our population of PerAF patients, non-PV triggers could be elicited in ∼70% of PerAF patients and their elimination significantly improved outcomes.

B-PO02-140 EFFECT OF ATRIAL ECTOPY COUPLING INTERVAL ON ATRIAL STRUCTURAL REMODELLING AND ATRIAL FIBRILLATION IN A SWINE MODEL

Frequent premature atrial complexes (PACs) are associated with incident atrial fibrillation (AF), however, the significance of PAC-coupling interval (CI) on atrial structural remodelling as well as development of AF is unknown. To investigate the impact of PAC-CI on atrial structural remodelling and AF inducibility in a swine model. Fifteen swine underwent pacemaker implantation to create a model of paced PACs (50% burden) from the lateral left atrium (LA) via the coronary sinus and were divided into 3 groups: (1) Short CI of 250ms (Short-CI: n=5), (2) Long CI of 400ms (Long-CI: n=5), and (3) controls without PACs (CTRL, n=5). At baseline and after 4 months of PACs, all swine underwent electrophysiologic (atrial ERP and AF induction with 50ms burst pacing) and echocardiographic studies (LA area and peak atrial longitudinal strain). Short-CI group had more LA enlargement compared with Long-CI and CTRL (terminal - baseline; Short-CI 7.0±0.9 vs. Long-CI 4.0±1.1 vs. CTRL 0.5±0.2 cm2; p<0.001). Both Short-CI and Long-CI group had a significant reduction in peak atrial longitudinal strain compared to CTRL (terminal - baseline; -22.8±9.7 vs. -18.3±3.7 vs. 0.1±4.5 %; p<0.001). No change in atrial ERP was observed (terminal - baseline; 3±20 vs -9 ±18 vs -5 ±34 ms; p=0.76). Short-CI group had the longest duration of burst pacing-induced AF (terminal - baseline; 71.2 [IQR 43.1, 102.9] vs. 34.3 [IQR 17.7, 61.0] vs. 5.3 [IQR 4.8, 9.7] secs; p=0.008). In a swine model, frequent PACs led to an atrial myopathy with heightened propensity to AF. Short-coupled PACs had a greater degree of structural remodelling and may contribute to the future development of AF.

Premature atrial complexes can predict atrial fibrillation in ischemic stroke patients: A systematic review and meta-analysis.

Several studies have explored premature atrial complexes (PACs) as high-risk factors for atrial fibrillation (AF) in ischemic stroke patients; however, the results were controversial. The aim of this systematic review and meta-analysis was to examine whether PACs can predict AF in ischemic stroke patients. We comprehensively searched the published literature in PubMed, Embase, and Wiley-Cochrane library databases from inception through August 18, 2020. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were analyzed by the fixed-effect model or the random-effect model based on heterogeneity. We identified 12 eligible studies including 2340 stroke patients with a mean age of 65.9 years. PACs were highly associated with AF occurrence in stroke (pooled OR: 4.16, 95% CI: 3.06-5.65) and cryptogenic stroke patients (pooled OR: 3.72, 95% CI: 2.66-5.20). Subgroup analysis showed PAC presence and frequent PACs were correlated with stroke in AF patients (pooled OR: 3.72, 95% CI: 1.65-8.36 and pooled OR: 5.12, 95% CI: 3.12-8.41, respectively). Frequent PACs were identified as the risks for asymptomatic AF (OR: 6.18, 95% CI: 3.23-11.83) and future AF occurrence (OR: 3.71, 95% CI: 2.62-5.26) in stroke patients. The definition of frequent PACs was inconsistent, and was >70 beats/24h based on Holter monitoring. PACs confer high risks for asymptomatic AF and future AF occurrence in stroke patients.

The relationship between premature atrial complexes and recurrence of atrial fibrillation: a meta-analysis

Objective: To explore the relationship between premature atrial complexes (PACs) and recurrence of atrial fibrillation (AF). Methods: Published literature was searched in PubMed, Embase, Web of Science, Cochrane, Weipu, China national knowledge infrastructure, Wanfang and China Biology Medicine disc up to 25 March 2020. RevMan5.3 software was used to analyzed the data and publication bias was performed by Stata 15.1. Results: A total of 8 studies were identified, including 1 252 AF patients with a mean age of 61.67 years, and male patients accounted for 70.6%. During follow-up, AF recurred in 425 cases. Meta-analysis showed that frequent PACs was an independent risk factor for recurrence of AF (HR=2.64, 95%CI:1.40-4.97). Subgroup analyses showed that PACs not only increasedthe risk of recurrence of AF after electrical cardioversion (HR=2.38, 95%CI:1.25-4.51), but also significantly increased the risk of recurrence of AF after catheter ablation cardioversion (HR=2.90, 95%CI:1.11-7.60). Conclusions: PACs is significantly associated with AF recurrence.

Frequent premature atrial complexes and risk of concurrent atrial fibrillation

Abstract Background Premature atrial complexes (PACs) predict incident atrial fibrillation (AF) in long-term follow-up studies. It is unclear whether frequent PACs on ambulatory ECG recordings indicate a higher likelihood of concurrent, undiagnosed AF. Furthermore, the reproducibility of a 24 h PAC count is unclear. Objectives To determine if frequent PACs on 24 h ambulatory ECG monitoring predicts concurrent AF during subsequent, prolonged ECG monitoring and to assess the diagnostic reliability of PAC counts on a 24 hour ECG recording. Methods AF was defined as ≥30 seconds of irregular rhythm without P waves, which was detected by a proprietary algorithm and manually verified. The proportion of AF occurrence during the remainder of the monitoring period was calculated for pre-specified levels of PACs during the first 24 h, and a function describing the association was fitted. The diagnostic reproducibility of a 24 h PAC count was assessed by calculating the likelihood of a PAC count ≥1000/day during the entire monitoring duration for prespecified PAC count levels during the first 24h. Results The study population comprised 20,973 patients (41% men, mean age 69.5 years) who had recorded an ambulatory ECG with a monitoring duration of 4–30 days in the United States during the year 2017 (median monitoring duration 16 days). AF was detected in 2,029 (9.7%) of patients and the median time to first occurrence of AF was 5 days. PAC frequency during the first 24 h was associated with AF during the monitoring period beyond the first 24 h, increasing steadily from 4.2% among those with 0–5 PACs, to a plateau around 17% among those with 250–1000 PACs per day and above. (Fig. 1A). The reproducibility of low PAC counts was good. Only 5.5% of patients with 0–5 PACs during the first 24 h of monitoring (31.8% of the population), had ≥1000 PACs on an alternate monitoring day. In contrast, among subjects with 100 PACs the probability of a day with ≥1000 PACs was close to 50% (Fig. 1B). Conclusion In patients undergoing ambulatory ECG monitoring, frequent PACs during the first 24 h indicate a higher likelihood of AF occurrence during subsequent days of monitoring. Less than 5 PACs during the first 24 h indicate a low probability of AF or frequent PACs on a subsequent day of ECG monitoring. Figure 1 Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): The Swedish Heart and Lung Foundation; The Swedish Heart and Lung Association

Atrial premature activity detected after an ischaemic stroke unveils atrial myopathy

Recent publications suggest that left atrial (LA) myopathy is a potential source of thromboembolism, independent of atrial fibrillation. We sought to investigate whether the presence of atrial premature activity after an ischaemic stroke is associated with LA remodelling and dysfunction, and might be a surrogate marker of LA myopathy. After an ischaemic stroke or a transient ischaemic attack, patients without known atrial fibrillation or overt heart disease were included prospectively in the study. All patients had a standard workup, including ambulatory Holter electrocardiogram monitoring and transthoracic echocardiography. In some patients, transoesophageal echocardiography was also performed. Anatomical and functional LA remodelling were assessed using minimal and maximal volumes and LA emptying fraction in two-dimensional and three-dimensional echocardiography. Patients were separated into two groups according to the burden of atrial premature complexes (APCs), measured by Holter electrocardiography. Among 148 eligible patients recruited from October 2015 to May 2016, 93 were included in the group with non-frequent APCs (nf-APC:<100 APCs/24hours) and 43 in the group with frequent APCs (f-APC:>100 APCs/24hours). Twelve patients had paroxysmal atrial fibrillation, and were not included in the statistical analysis. Maximal and minimal indexed LA volumes were significantly higher in the f-APC group than in the nf-APC group (P<0.01). LA emptying fraction was worse in the f-APC group than in the nf-APC group. In addition, LA appendage emptying velocity was impaired in the f-APC group, and was correlated with LA remodelling variables, especially LA emptying fraction (r=0.621). After an ischaemic stroke or a transient ischaemic attack, excessive APCs are associated with LA remodelling. Thus, LA dilatation and dysfunction reflect early LA myopathy, which might itself be responsible for cardioembolic stroke.

Deep Learning Approaches to Detect Atrial Fibrillation Using Photoplethysmographic Signals: Algorithms Development Study.

BackgroundWearable devices have evolved as screening tools for atrial fibrillation (AF). A photoplethysmographic (PPG) AF detection algorithm was developed and applied to a convenient smartphone-based device with good accuracy. However, patients with paroxysmal AF frequently exhibit premature atrial complexes (PACs), which result in poor unmanned AF detection, mainly because of rule-based or handcrafted machine learning techniques that are limited in terms of diagnostic accuracy and reliability.ObjectiveThis study aimed to develop deep learning (DL) classifiers using PPG data to detect AF from the sinus rhythm (SR) in the presence of PACs after successful cardioversion.MethodsWe examined 75 patients with AF who underwent successful elective direct-current cardioversion (DCC). Electrocardiogram and pulse oximetry data over a 15-min period were obtained before and after DCC and labeled as AF or SR. A 1-dimensional convolutional neural network (1D-CNN) and recurrent neural network (RNN) were chosen as the 2 DL architectures. The PAC indicator estimated the burden of PACs on the PPG dataset. We defined a metric called the confidence level (CL) of AF or SR diagnosis and compared the CLs of true and false diagnoses. We also compared the diagnostic performance of 1D-CNN and RNN with previously developed AF detectors (support vector machine with root-mean-square of successive difference of RR intervals and Shannon entropy, autocorrelation, and ensemble by combining 2 previous methods) using 10 5-fold cross-validation processes.ResultsAmong the 14,298 training samples containing PPG data, 7157 samples were obtained during the post-DCC period. The PAC indicator estimated 29.79% (2132/7157) of post-DCC samples had PACs. The diagnostic accuracy of AF versus SR was 99.32% (70,925/71,410) versus 95.85% (68,602/71,570) in 1D-CNN and 98.27% (70,176/71,410) versus 96.04% (68,736/71,570) in RNN methods. The area under receiver operating characteristic curves of the 2 DL classifiers was 0.998 (95% CI 0.995-1.000) for 1D-CNN and 0.996 (95% CI 0.993-0.998) for RNN, which were significantly higher than other AF detectors (P<.001). If we assumed that the dataset could emulate a sufficient number of patients in training, both DL classifiers improved their diagnostic performances even further especially for the samples with a high burden of PACs. The average CLs for true versus false classification were 98.56% versus 78.75% for 1D-CNN and 98.37% versus 82.57% for RNN (P<.001 for all cases).ConclusionsNew DL classifiers could detect AF using PPG monitoring signals with high diagnostic accuracy even with frequent PACs and could outperform previously developed AF detectors. Although diagnostic performance decreased as the burden of PACs increased, performance improved when samples from more patients were trained. Moreover, the reliability of the diagnosis could be indicated by the CL. Wearable devices sensing PPG signals with DL classifiers should be validated as tools to screen for AF.

Frequent premature atrial complexes as a marker of occult atrial fibrillation in patients with stroke

Frequent premature atrial complexes as a marker of occult atrial fibrillation in patients with stroke

Features of Patients Aged 80 Years or Older with Embolic Stroke of Undetermined Source

Background: Embolic stroke of undetermined source has not been thoroughly investigated in older patients. In this study, we investigated the features of this condition in patients greater than or equal to 80 years of age. Methods: All patients with acute ischemic stroke in our hospital underwent diffusion-weighted imaging, magnetic resonance angiography, T2-weighted imaging, and fluid-attenuated inversion recovery sequence imaging. Embolic stroke of undetermined source was defined as a radiologically confirmed nonlacunar brain infarct on diffusion-weighted imaging without (1) extracranial or intracranial atherosclerosis causing greater than or equal to 50% luminal stenosis in arteries supplying the ischemic area, (2) major-risk cardioembolic source, and (3) any other specific cause of stroke. We retrospectively identified consecutive patients hospitalized for acute ischemic stroke who met the embolic stroke of undetermined source diagnostic criteria and investigated patients’ baseline and diagnostic findings. Results: We divided 122 consecutive embolic stroke of undetermined source patients (median age: 73 years; 49 men, 73 women) into 2 groups by age at admission. Patients aged greater than or equal to 80 years had higher D-dimer and brain natriuretic peptide levels, more frequent premature atrial complexes/day in 24-hour Holter electrocardiography, and thicker maximum intima media thickness on ultrasound compared with patients aged less than 80 years (P < .05, U test). Conclusions: Our results suggest that high admission D-dimer and brain natriuretic peptide levels are associated with age of onset in patients with embolic stroke of undetermined source. Patients aged greater than or equal to 80 years tended to have more frequent premature atrial complexes and thicker maximum intima media thickness compared with patients aged less than 80 years.

Frequent premature atrial complexes as a predictor of atrial fibrillation: Systematic review and meta-analysis

BackgroundFrequent premature atrial complexes (PACs) are associated with higher morbidity and mortality. Recent studies suggest that frequent PACs are associated with new onset atrial fibrillation (AF). However, a systematic review and meta-analysis of the literature has not been done. We assessed the association between frequent PACs and new onset AF by a systematic review and a meta-analysis. MethodsWe comprehensively searched the databases of MEDLINE and EMBASE from inception to September 2017. Included studies were published cohort (prospective or retrospective) that compared new onset AF among patients with and without frequent PACs documented by Holter monitoring or 12-lead electrocardiogram. Data from each study were combined using the random-effects, generic inverse variance method of DerSimonian and Laird to calculate risk ratios and 95% confidence intervals. ResultsTwelve studies from 2009 to 2017 were included in this meta-analysis involving 109,689 subjects (9217frequent and 100,472 non-frequent PACs). Frequent PACs were associated with increased risk of new onset AF (pooled risk ratio = 2.76, 95% confidence interval: 2.05–3.73, p < 0.000, I2 = 90.6%). ConclusionFrequent PACs are associated with up to three-fold increased risk of new onset AF. Our study suggests that frequent PACs in general population is an independent predictor of new onset AF.