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Background: Unknown cardioembolic sources are frequent causes of cryptogenic stroke. We analyzed the risk of atrial fibrillation (AF) or high burden of ectopic atrial activity (HBEA) in patients with cryptogenic stroke, assessing atrial function and 1-year outcomes., Methods and Results: The ARIES (Atrial Imaging and Cardiac Rhythm in Cryptogenic Embolic Stroke) study is an observational study including patients with cryptogenic stroke. We analyzed the frequency of AF and HBEA (>3000 atrial ectopic beats/day or >2 bursts or atrial tachycardia between 3 beats and ≤30 seconds) in two 30-day Holter-ECGs, comparing advanced echocardiography signs of left atrial (LA) dysfunction according to rhythm: AF, HBEA, and normal sinus rhythm. We also evaluated 1-year stroke recurrence and mortality. The study included 109 patients; 35 (32.1%) patients had AF, 27 (24.8%) HBEA, and 47 (43.1%) normal sinus rhythm. Compared with those with normal sinus rhythm, patients with AF presented higher 2-dimensional and 3-dimensional LA indexed volumes (38.8±11.2 versus 27.3±11.8 mL/m 2 , and 50.6±17.2 versus 34.0±15.4 mL/m 2 , respectively, P <0.001), lower 3-dimensional LA ejection fraction (50±14.6 versus 62.7±11.8, P =0.001), LA reservoir strain (22.0±8.6 versus 30.4±10.5, P <0.001), and LA contraction strain (10.5±8.18 versus 17.1±7.5, P <0.001), remaining significant in multivariate analysis. Patients with HBEA showed higher LA indexed volumes and lower LA reservoir strain than patients with normal sinus rhythm only in univariate analysis. There were no differences in ischemic recurrence or mortality among the groups., Conclusions: Patients with cryptogenic stroke showed a high incidence of AF and HBEA. AF is strongly related to LA volume, LA function, and LA reservoir and contraction strain, whereas HBEA showed milder structural changes. Advanced LA echocardiography could help patient selection for long-term ECG monitoring in suspected cardiac sources.

BACKGROUND Paroxysmal third-degree atrioventricular block (AVB) can exhibit a vast array of symptoms, but commonly, paroxysmal AVB leads to presyncope, syncope, or possibly sudden cardiac death. We present a rare case of pause-dependent paroxysmal AVB that was triggered by a premature atrial contraction. CASE REPORT A 65-year-old man with frequent episodes of presyncope and syncope for 3 weeks was admitted to our hospital for further diagnosis. A resting 12-lead electrocardiogram showed an incomplete right bundle branch block, and a 24-h Holter recording showed multiple episodes of third-degree AVB. Intracardiac tracing revealed that the block site was distal, at the infra-His-Purkinje system. CONCLUSIONS This case highlights a rare case of pause-dependent paroxysmal AVB that was triggered by a premature atrial contraction. This type of AVB is an abrupt, unexpected, repetitive block of atrial impulses as they propagate to the ventricles. It is relatively rare, and due to its transient nature, it is often under recognized and can lead to sudden cardiac death.

Background: Covert atrial fibrillation (AF) is a major cause of cryptogenic stroke. This study investigated whether a dose-dependent relationship exists between the frequency of premature atrial contractions (PACs) and AF detection in patients with cryptogenic stroke using an insertable cardiac monitor (ICM)., Methods: We enrolled consecutive patients with cryptogenic stroke who underwent ICM implantation between October 2016 and September 2020 at 8 stroke centers in Japan. Patients were divided into 3 groups according to the PAC count on 24-hour Holter ECG: ≤200 (group L), >200 to ≤500 (group M), and >500 (group H). We defined a high AF burden as above the median of the cumulative duration of AF episodes during the entire monitoring period. We evaluated the association of the frequency of PACs with AF detection using log-rank trend test and Cox proportional hazard model and with high AF burden using logistic regression model, adjusting for age, sex, CHADS 2 score., Results: Of 417 patients, we analyzed 381 patients with Holter ECG and ICM data. The median age was 70 (interquartile range, 59.5-76.5), 246 patients (65%) were males, and the median duration of ICM recording was 605 days (interquartile range, 397-827 days). The rate of new AF detected by ICM was higher in groups with more frequent PAC (15.5%/y in group L [n=277] versus 44.0%/y in group M [n=42] versus 71.4%/y in group H [n=62]; log-rank trend P <0.01). Compared with group L, the adjusted hazard ratios for AF detection in groups M and H were 2.11 (95% CI, 1.24-3.58) and 3.23 (95% CI, 2.07-5.04), respectively, and the adjusted odds ratio for high AF burden in groups M and H were 2.57 (95% CI, 1.14-5.74) and 4.25 (2.14-8.47), respectively., Conclusions: The frequency of PACs was dose-dependently associated with AF detection in patients with cryptogenic stroke., Competing Interests: Disclosures Dr Todo reports lecture fees from Pfizer, Bristol-Myers Squibb, Daiichi-Sankyo, Bayer, Medtronic, Abbott, and Otsuka Pharmaceutical. Dr Doijiri reports lecture fees from Medtronic, Abbott, Biotronic, Daiichi Sankyo, Bristol-Myers Squibb, and Bayer. Dr Yamazaki reports lecture fees from Medtronic, Abbott, Daiichi Sankyo, Bristol-Myers Squibb, and Bayer. Dr Iwata reports lecture fees from Daiichi-Sankyo, and Medtronic. Dr Sonoda reports lecture fees from Medtronic, Abbott, and Daiichi-Sankyo. Dr Koge reports lecture fees from Medtronic. Dr Koga reports honoraria from Daiichi-Sankyo and research support from Daiichi-Sankyo. Dr Nagata reports lecture fees from Otsuka Pharmaceutical, Daiichi-Sankyo, Eli Lilly, and Amgen. Dr Ueno reports research funds from Bristol-Myers Squibb. Dr Yamagami reports lecture fees from Medtronic, Abbott, Daiichi-Sankyo, Bristol-Myers Squibb, and Bayer, and grant support from Bristol-Myers Squibb. Dr Gon reports lecture fees from Eisai, Kyowa Kirin, and Pfizer. The other authors report no conflicts.

Although increased premature atrial contractions (PACs) reportedly predict atrial fibrillation (AF) in both general and specific (e.g., patients with stroke) populations, early postoperative AF (POAF) risk in patients with increased PAC burden who require cardiac surgery remains unclear. We examined the correlation between different preoperative PAC burdens and POAF in patients with obstructive hypertrophic cardiomyopathy (OHCM) who underwent surgical treatment. We analyzed 304 consecutively admitted patients with OHCM without previous AF who underwent isolated septal myectomy between January 2015 and December 2018. All patients underwent preoperative 24-hour Holter electrocardiogram monitoring. PACs were present in 259 patients (85.20%) and absent in 45 patients (14.80%). According to the cut-off PAC number of 100 beats/24 hours, there were 211 patients (69.41%) with low-burden PACs and 48 patients (15.79%) with high-burden PACs. AF after septal myectomy occurred in 73 patients, which consisted of 3/45 in the non-PAC group (6.67%), 47/211 in the low-PAC-burden group (22.27%), and 23/48 in the high PAC burden group (47.92%). POAF incidence was higher in both low- and high-burden patients than in patients without PAC (p <0.01). Multivariate logistic regression analyses demonstrated that high-burden PACs (p = 0.02) and age (p <0.01) but not low-burden PACs (p = 0.22) independently predicted POAF in patients with OHCM. The area under the receiver operating characteristic curve for preoperative PACs was 0.72 (95% confidence interval 0.66 to 0.79, p <0.01, sensitivity: 68.49%, specificity: 69.26%). In conclusion, POAF incidence was significantly higher in patients with preoperative high-burden PACs and can predict POAF in patients with OHCM., Competing Interests: Disclosures The authors have no conflicts of interest to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: The prevalence and nature of cardiac complications associated with hyperthyroidism vary considerably in the literature depending on the population studied and the means of investigation used to detect them. The aim of this study was to determine the structural, functional, and rhythmic cardiac abnormalities associated with hyperthyroidism and to identify their risk factors., Methods: It is a cross-sectional study conducted in thirty adult patients with overt or subclinical hyperthyroidism. Each patient underwent a clinical cardiovascular examination, a cardiac Doppler ultrasound, a pulmonary ultrasound and a 24-hours rhythm holter. The diagnosis of cardiothyreosis (thyrotoxic heart disease) was retained if an arrhythmia, heart failure (HF) and/or pulmonary arterial hypertension (PAH) were noted following the investigations carried out., Results: The mean age of the patients was 44.8 ± 14.4 years. The sex ratio (M/F) was 0.3. Five patients (17%) had subclinical hyperthyroidism and 25 (83%) had overt hyperthyroidism. Thirteen patients (43%) had cardiothyreosis. It consisted of a rhythm disorder in three patients (10%), PAH in twelve patients (40%) and HF in eight patients (27%). An age over 50 years and toxic nodular etiology were associated with atrial fibrillation (AF), p = 0.041 and p = 0.004 respectively. Tachycardia and a higher number of atrial extrasystoles were associated with HF, p = 0.039 and p = 0.007 respectively. A lower TSH, tachycardia and a higher number of atrial extrasystoles were associated with the presence of PAH, p = 0.004, p = 0.011 and p = 0.007 respectively., Conclusion: Cardiac complications should be sought in all patients with hyperthyroidism, especially in elderly and tachycardic patients. Specialized investigations such as echocardiography or 24 hours rhythmic holter should be requested in these cases., Competing Interests: Déclaration de liens d'intérêts Les auteurs déclarent n'avoir aucun lien d'intérêt en relation avec cet article Aucun, (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Premature atrial contractions are a common cardiac phenomenon. Although previously considered a benign electrocardiographic finding, they have now been associated with a higher risk of incident atrial fibrillation (AF) and other adverse outcomes such as stroke and all-cause mortality. Since premature atrial contractions can be associated with these adverse clinical outcomes independently of AF occurrence, different explanations have being proposed. The concept of atrial cardiomyopathy, where AF would be an epiphenomenon outside the causal pathway between premature atrial contractions and stroke has received traction recently. This concept suggests that structural, functional, and biochemical changes in the atria lead to arrhythmia occurrence and thromboembolic events. Some consensus about diagnosis and treatment of this condition have been published, but this is based on scarce evidence, highlighting the need for a clear definition of excessive premature atrial contractions and for prospective studies regarding antiarrhythmic therapies, anticoagulation or molecular targets in this group of patients., Competing Interests: Conflict of interest: J.M.F.: none declared; D.G.: institutional research grants from Boston Scientific, Medtronic and Biosense Webster, and personal advisory fees from Boehringer Ingelheim, Boston Scientific and Abbott; G.Y.H.L.: consultant and speaker for BMS/Pfizer, Boehringer Ingelheim and Daiichi-Sankyo. No fees are received personally., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Marijuana use among all age groups has been increasing, including among older adults aged ≥65 years. There is a lack of epidemiologic data examining arrhythmia risk among users of marijuana. We evaluated cross-sectional associations between current and past marijuana smoking and arrhythmias among 1485 participants from the Multiethnic Study of Atherosclerosis who underwent extended ambulatory electrocardiographic monitoring with the Zio Patch XT. Outcomes included premature atrial contractions, runs of supraventricular tachycardia, premature ventricular contractions, and runs of nonsustained ventricular tachycardia (NSVT). Compared with never users, participants reporting current use of marijuana (n = 40, 3%) had more supraventricular tachycardia/day (adjusted geometric mean ratio [GMR] 1.42, 95% confidence interval [CI] 0.87 to 2.32), more premature atrial contractions/hour (GMR 1.22, 95% CI 0.72, 2.13), and more NSVT/day (GMR 1.28, 95% CI 0.95 to 1.73); although, CIs overlapped 1. Additionally, more frequent marijuana use was associated with more runs of NSVT/day (GMR 1.56, 95% CI 1.13, 2.17). In conclusion, our results suggest that current marijuana use may be associated with a greater burden of arrhythmias. There is a need for additional research, mainly using a prospective design, to clarify if marijuana use causes atrial and ventricular arrhythmias or other cardiovascular complications among older adults., Competing Interests: Disclosures BMS reports grant funding from the National Institutes of Health related to the content of this study, and the Canadian Institutes of Health Research, the Quebec Health Research Fund, the Canadian Lung Association, and the Quebec Lung Association. All authors report funding from the National Institutes of Health during the conduct of this study., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Machine learning and deep learning techniques are now used extensively for atrial fibrillation (AF) screening, but their use for AF crisis forecasting has yet to be assessed in a clinical context., Aims: To assess the value of two machine learning algorithms for the short-term prediction of paroxysmal AF episodes., Methods: We conducted a retrospective study from an outpatient clinic. We developed a deep neural network model that was trained for a supervised binary classification, differentiating between RR interval variations that precede AF onset and RR interval variations far from any AF. We also developed a random forest model to obtain forecast results using heart rate variability variables, with and without premature atrial complexes., Results: In total, 10,484 Holter electrocardiogram recordings were screened, and 250 analysable AF onsets were labelled. The deep neural network model was able to distinguish if a given RR interval window would lead to AF onset in the next 30 beats with a sensitivity of 80.1% (95% confidence interval 78.7-81.6) at the price of a low specificity of 52.8% (95% confidence interval 51.0-54.6). The random forest model indicated that the main factor that precedes the start of a paroxysmal AF episode is autonomic nervous system activity, and that premature complexes add limited additional information. In addition, the onset of AF episodes is preceded by cyclical fluctuations in the low frequency/high frequency ratio of heart rate variability. Each peak is itself followed by an increase in atrial extrasystoles., Conclusions: The use of two machine learning algorithms for the short-term prediction of AF episodes allowed us to confirm that the main cause of AF crises lies in an imbalance in the autonomic nervous system, and not premature atrial contractions, which are, however, required as a final firing trigger., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Background: The contribution of left atrial disease and excessive supraventricular ectopic activity (ESVEA) to the risk for incident atrial fibrillation (AF) is incompletely understood., Objective: To analyse the ten-year risk to develop AF in patients with cardiovascular risk factors and to define the impact of parameters of left atrial disease and ESVEA on AF risk., Methods: 148 patients from the Diast-CHF trial with at least one cardiovascular risk factor and free of AF at baseline were followed for 10 years. Left atrial disease was defined as left atrial volume index (LAVI) >35 ml/m2, P-terminal force in lead V1 (PTFV1) >4000 ms*μV or elevated N-terminal pro-B-type natriuretic peptide (NT-proBNP) >250 pg/ml. We analyzed the association of these parameters and ESVEA (either >720 premature atrial contractions (PAC) or one atrial run >20 beats per day) on AF-free survival., Results: After ten years, AF was newly detected in twelve patients (13.4%) with signs of left atrial disease and two patients (3.4%) without signs of left atrial disease (p = 0.04). LAVI (p = 0.005), ESVEA (p = 0.016) and NT-proBNP (p = 0.010) were significantly associated with AF-free survival in univariate analysis. A combined Cox model of left atrial disease parameters showed associations for NT-proBNP (HR 3.56; 95%CI 1.33-5.31; p = 0.04) and PAC (HR 2.66; 95%CI 1.25-10.15; p = 0.01) but not for LAVI or PTFV1 with AF-free survival., Conclusion: The risk for AF is higher in patients with cardiovascular risk factors and signs of left atrial disease. NT-proBNP and premature atrial contractions independently predict AF-free survival. The role of excessive supraventricular ectopic activity for the assessment of AF risk may be underestimated and requires further study., Competing Interests: The authors have declared that no competing interests exist.

Background and Purpose: 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., Methods: 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., Results: 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/24 h based on Holter monitoring., Conclusions: PACs confer high risks for asymptomatic AF and future AF occurrence in stroke patients., (© 2021 Wiley Periodicals LLC.)

Premature atrial complexes (PACs) have been suggested to increase the risk of adverse events. The distribution of PAC burden and its dose-response effects on all-cause mortality and cardiovascular death had not been elucidated clearly. We analyzed 15,893 patients in a medical referral center from July 1st, 2011, to December 31st, 2018. Multivariate regression driven by ln PAC (beats per 24 h plus 1) or quartiles of PAC burden were examined. Older group had higher PAC burden than younger group (p for trend < 0.001), and both genders shared similar PACs distribution. In Cox model, ln PAC remained an independent risk factor for all-cause mortality (hazard ratio (HR) = 1.09 per ln PAC increase, 95% CI = 1.06‒1.12, p < 0.001). PACs were a significant risk factor in cause-specific model (HR = 1.13, 95% CI = 1.05‒1.22, p = 0.001) or sub-distribution model (HR = 1.12, 95% CI = 1.04‒1.21, p = 0.004). In ordinal PAC model, 4th quartile group had significantly higher risk of all-cause mortality than those in 1st quartile group (HR = 1.47, 95% CI = 1.13‒1.94, p = 0.005), but no difference in cardiovascular death were found in competing risk analysis. In subgroup analysis, the risk of high PAC burden was consistently higher than in low-burden group across pre-specified subgroups. In conclusion, PAC burden has a dose response effect on all-cause mortality and cardiovascular death.

Background: Atrial fibrillation (AF) in heart failure (HF) patients has been associated with a worse outcome. Similarly, excessive supraventricular ectopic activity (ESVEA) has been linked to development of AF, stroke, and death. This study aimed to investigate AF and ESVEA's association with outcomes and effect of prophylactic implantable cardioverter defibrillator (ICD) implantation in nonischemic HF patients., Methods: A total of 850 patients with nonischemic HF, left ventricle ejection fraction ≤35%, and elevated N-terminal pro-brain natriuretic peptides underwent 24 hours Holter recording. The presence of AF (≥30 seconds) and ESVEA (≥30 supraventricular ectopic complexes (SVEC) per hour or run of SVEC ≥20 beats) were registered. Outcomes were all-cause mortality, cardiovascular death (CVD), and sudden cardiac death (SCD)., Results: AF was identified in 188 patients (22%) and ESVEA in 84 patients (10%). After 4 years and 11 months of follow-up, a total of 193 patients (23%) had died. AF was associated with all-cause mortality (hazard ratio [HR] 1.44; confidence interval [CI] 1.04-1.99; P = .03) and CVD (HR 1.59; CI 1.07-2.36; P = .02). ESVEA was associated with all-cause mortality (HR 1.73; CI 1.16-2.57; P = .0073) and CVD (HR 1.76; CI 1.06-2.92; P = .03). Neither AF nor ESVEA was associated with SCD. ICD implantation was not associated with an improved prognosis for neither AF (P value for interaction = .17), nor ESVEA (P value for interaction = .68)., Conclusions: Both AF and ESVEA were associated with worsened prognosis in nonischemic HF. However, ICD implantation was not associated with an improved prognosis for either group., (Copyright © 2020 Elsevier Inc. All rights reserved.)

In cryptogenic stroke patients, early detection of new-onset atrial fibrillation (AF) and recurrent stroke is required to prevent poor clinical outcomes. Therefore, we investigated the predictors of new-onset AF and recurrent stroke in cryptogenic stroke patients without previously diagnosed AF. In total, 390 patients who were diagnosed with stroke and non-sustained atrial tachycardia (NSAT) on 24-hour Holter monitoring were followed up to assess new-onset AF and recurrent stroke. The 5-year event-free survival as well as the predictors of recurrent stroke or new-onset AF were investigated. Based on receiver operating characteristic analysis, frequent premature atrial contractions (PACs) were defined as PACs >44 beats/day. The median follow-up period was 35 months. The composite event rate was 11.5%. In Kaplan-Meier analysis, the 5-year cumulative incidence of composite events was higher in cryptogenic stroke patients with frequent PACs than in those without frequent PACs. Multivariate analysis revealed that current smoking, increased left atrial volume index, and frequent PACs were poor prognostic predictors of composite event, and frequent PACs were an independent poor prognostic factor of new-onset AF in cryptogenic stroke patients. Therefore, frequent PACs might be associated with poor clinical outcomes (new-onset AF and recurrent stroke) in cryptogenic stroke patients with concomitant NSAT., Competing Interests: The authors have no potential conflicts of interest to disclose., (© Copyright: Yonsei University College of Medicine 2020.)

Background: Frequent premature atrial contractions (PACs) are associated with atrial fibrillation, stroke, and mortality. However, the cut-off value for PAC counts that could identify patients with different stroke features is unclear, and the association of PACs to outcome is not determined., Methods: The study retrospectively included patients with acute ischemic stroke who had underwent both a 24 h Holter recording and a brain MRI in Taipei Veterans General Hospital from January 2015 to May 2016. Patients were categorized into four groups according to their PAC frequencies on 24 h Holter recording. We compared the clinical severity, neuroimage features, stroke subtypes, and functional outcome among the four groups of patients., Results: Among the 278 patients, the lower, middle, and upper quartiles of the PAC counts were 23, 74, and 459.5, respectively. In contrast to the 1 st quartile of patients, the 3 rd (PAC 75-459/24 h) and the 4 th (PAC ≥460/24 h) quartiles of patients had higher NIH Stroke Scale (NIHSS) at admission (p = 0.014 and p = 0.002, respectively). The frequencies of cryptogenic stroke were not different among the 4 quartiles of the patients, but cryptogenic stroke patients with ≥ 75PACs/24hours had higher stroke severity compared to those with PACs < 75counts/24 h (NIHSS 9.1 vs. 5.2, p = 0.043). There was an increased trend in infarcts of multiple vascular territories and in mortality at 1 year among the four groups of patients with increased PAC frequency (p = 0.045 and p = 0.002, respectively). The 4 th PAC quartile was associated with poor functional outcome (modified Rankin Scale ≥ 4) at 3 months in univariate analysis (OR: 5.66, CI: 2.69-11.91, p < 0.001), but was not an independent predictor after controlling for initial stroke severity., Conclusions: PACs ≥ 75 counts/24 h was associated with higher clinical severity in patients with acute ischemic stroke., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The frequency of premature atrial complexes (PACs) has been related with atrial fibrillation (AF) occurrence and adverse prognosis. Research objective was to evaluate whether temporal patterns of PACs are directly associated with AF onset in pacemaker patients with continuous monitoring of the atrial rhythm. Overall, 193 pacemaker patients (49% female, 72 ± 9 years old), enrolled in a national registry, were analyzed. Frequency of daily PACs was measured in a 14-day initial observation period, during which patients were in sinus rhythm. In the following period, temporal occurrence and frequency of daily PACs and eventual onset of AF were derived by pacemaker diagnostics. In the run-in period, median PACs frequency was 614 PACs/day (interquartile range 70-3056). Subsequently, in a median follow-up of 6 months, AF occurred in 109 patients, in particular in 37/96 (38.5%) patients with a PAC rate < 614 PACs/day and in 72/97 (74.2%) patients with PAC rate ≥ 614 PACs/day (p < 0.001). In patients with AF occurrence, the number of daily PACs, normalized by dividing for the average of PACs in ten preceding days, progressively increased in the 5 days preceding AF. Cox model predictive analysis showed that the risk of AF was significantly higher in patients with a relative increase of the daily PACs higher than 30% compared with PACs average number in ten preceding days [hazard ratio (95% confidence interval) 3.67 (2.40-5.59), p < 0.001]. PACs frequency increases in the 5 days preceding AF onset. A relative increase of the daily PACs is significantly associated with the risk of AF occurrence.

Background: Catheter-based renal sympathetic denervation (RDN) can reduce sympathetic activity and blood pressure (BP) in patients with hypertension. The present study aimed at investigating the effects of RDN on heart rate (HR), number of premature captions, and heart rate variability (HRV)., Methods: A total of 105 patients (67% male, age 63.5 ± 10 years) with resistant hypertension (BP 169 ± 22/89 ± 14 mmHg) underwent bilateral RDN using a radiofrequency catheter (Symplicity Flex, Medtronic). 24-h Holter monitoring was performed at baseline and after 6 months. Besides HR profile, the number of premature atrial (PAC) and ventricular captions (PVC), time and frequency domain-based HRV were analyzed. Data are presented as mean ± standard deviation or median (interquartile range)., Results: Office systolic and diastolic BP were reduced after RDN by 21.8 ± 25.2 mmHg and 8 ± 18.7 mmHg (p < 0.001 for both), respectively. Twenty-eight (27%) patients had a reduction of < 10 mmHg in systolic BP. At baseline, mean 24-h HR was 65.7 ± 9.9 bpm. The prevalence of PAC [median 1.2 (0.3-6.2)] and PVC [median 1.2 (0.1-13.9)] was low and values of HRV were within normal limits and not different between responders and non-responders. After 6 months, patients with a baseline HR > 72 min had a significant reduction in HR by 2.3 ± 7.1 bpm. Parameters of HRV did not significantly change during follow-up. In patients with ≥ 6 PAC per hour at baseline, a significant median reduction of - 12.4 (- 37.4 to - 2.3) PAC after 6 months was documented (p = 0.002), which occurred independently from BP effects. The number of PVC was not significantly altered after RDN., Conclusion: In patients with resistant hypertension and elevated HR or high burden of PACs, RDN was associated with a reduction of HR and number of PAC. Parameters of HRV were not changed after RDN nor were predictive of response to RDN.

Patients with hypertension who develop atrial premature complexes (APCs) are at a particularly high risk for atrial fibrillation (AF). We sought to identify medications and modifiable risk factors that could reduce the risk of AF imposed by presence of APCs in such a high risk group. This analysis included 4,331 participants with treated hypertension from the Reasons for Geographic and Racial Differences in Stroke study who were free of AF and cardiovascular disease at the time of enrollment (2003-2007). APCs were detected in 8.2% (n = 356) of the participants at baseline. During a median follow-up of 9.4 years, 9.9% (n = 429) of the participants developed AF. Participants with APCs, compared with those without, were more than twice as likely to develop AF (Odds ratio [95% confidence interval]: 2.36[1.75, 3.19]). This association was significantly weaker in statin users than nonusers (Odds ratio [95% confidence interval]:1.42[0.81,2.48] vs 3.01[2.11,4.32], respectively; interaction p-value = 0.02), and in angiotensin-II receptor blocker users than nonusers (Odds ratio [95% confidence interval]:1.31[0.66,2.61] vs 2.78[1.99,3.89], respectively; interaction p-value = 0.05). Borderline weaker associations between APCs and AF were also observed in alpha-blocker users than nonusers, nondiabetics than diabetics, and in those with systolic blood pressure level 130 to 139 mm Hg compared with those with other systolic blood pressure levels. No significant effect modifications were observed by use of other medications or by presence of other cardiovascular risk factors. In conclusion, the significant AF risk associated with APCs in patients with hypertension could potentially be reduced by treatment with angiotensin-II receptor blockers and statins along with lowering blood pressure and management of diabetes., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Although previous studies reported frequent premature atrial contractions(fPACs) increased the risk of adverse cardiovascular outcomes, especially atrial fibrillation(AF), there is a substantial inconsistency between reports concerning the definition of fPAC. In this study, we aimed to investigate the relationship between fPAC and cardiovascular outcomes, especially AF. We further searched for a cutoff value of fPAC for prediction of AF., Methods: We retrospectively analyzed the ambulatory 24-hr Holter monitoring records and 392 patients included. Frequent PAC was defined as more than 720 PAC/24 hr as used for frequent ventricular premature beats. Patients' baseline characteristics, echocardiographic variables and medical history were recorded., Results: There were 189 patients with fPAC and 203 patients without fPAC. Patients with fPAC had more comorbidities in terms of hypertension, diabetes mellitus, coronary artery disease and congestive heart failure. CHA2DS2-VaSc was higher in patients with fPAC. Mean follow-up duration was 31 months, and the number of patients with new-onset AF during follow-up was significantly higher in fPAC group (22% vs. 5%, p < .001). fPAC was significantly and independently associated with new-onset AF and predicted AF with a cutoff value of 3,459 PAC/24 hr, and the risk of AF was 11-fold higher than those with <3,000 PAC/24 hr. In addition, an increased CHA2DS2-VaSc score was also associated with new-onset atrial fibrillation., Conclusion: In our study, we have demonstrated that fPAC is significantly associated with new-onset AF, and this association is the strongest among those patients who have more than 3,000 PAC in 24 hr., (© 2019 The Authors. Annals of Noninvasive Electrocardiology published by Wiley Periodicals, LLC.)

The relationship between atrial fibrillation (AF) type and stroke risk is still controversial. We investigated the difference of burden of atrial ectopic beats in different types of AF and the effect of the AF type on stroke risk in patients with non-valvular AF. In the prospective, multicenter observational registry with more than about 10,000 AF patients, 8883 non-valvular AF patients (mean age, 67.0 years; 36% were women) with eligible follow-up visits participated. We compared the burden of ectopic beats and stroke risk between patients with paroxysmal AF (n = 5,808) and non-paroxysmal AF (n = 3,075). The patients with a non-paroxysmal type of AF were older, male-predominant and had a higher prevalence of comorbidities and had more anticoagulation and rhythm control treatment than those with paroxysmal AF. In terms of the difference in burden of ectopic beats, patients with non-paroxysmal AF had a higher proportion of atrial premature beats (APBs) (paroxysmal vs. non-paroxysmal, median 3% vs. 5%; p = 0.001) in 24 hours Holter monitoring. During a median follow-up period of 16.8 months (Interquartile range [IQR], 11.67-20.52), a total of 82 (0.92%) patients experienced ischemic stroke with incidence rates of 0.50 and 1.09 events per 100 person-year for paroxysmal and non-paroxysmal AF, respectively. The cumulative incidence of stroke events was significantly higher in non-paroxysmal AF than in paroxysmal AF (p < 0.001). The risk of ischemic stroke was higher in non-paroxysmal AF with an adjusted hazard ratio (HR) of 2.08 (95% confidence interval [CI], 1.33-3.25; p = 0.001) than in paroxysmal AF. The type of AF was associated with an increased risk of stroke, along with the difference of burden of ectopic beats (specially in APBs) in different types of AF. These results suggest that the type of AF should be considered in stroke prevention and decision-making for oral anticoagulation in AF patients.

Background: Recent publications suggest that left atrial (LA) myopathy is a potential source of thromboembolism, independent of atrial fibrillation., Aims: 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., Methods: 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., Results: 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)., Conclusions: 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., (Copyright © 2020. Published by Elsevier Masson SAS.)

Objective: To determine whether frequent premature atrial contractions (PAC) predict atrial fibrillation (AF) in cryptogenic stroke patients, we analyzed the association between frequent PACs in 24-h Holter electrocardiogram recording and AF detected by insertable cardiac monitoring (ICM)., Methods: We retrospectively analyzed a database of 66 consecutive patients with cryptogenic stroke who received ICM implantation between October 2016 and March 2018 at 5 stroke centers. We included the follow-up data until June 2018 in this analysis. We defined frequent PACs as the upper quartile of the 66 patients. We analyzed the association of frequent PACs with AF detected by ICM., Results: Frequent PACs were defined as >222 PACs per a 24-h period. The proportion of patients with newly detected AF by ICM was higher in patients with frequent PACs than those without (50% [8/16] vs. 22% [11/50], p < 0.05). Frequent PACs were associated with AF detection and time to the first AF after adjustment for CHADS2 score after index stroke, high plasma -B-type natriuretic peptide (BNP; >100 pg/mL) or serum -N-terminal pro-BNP levels (>300 pg/mL), and large left atrial diameter (≥45 mm)., Conclusion: High frequency of PACs in cryptogenic stroke may be a strong predictor of AF detected by ICM., (© 2020 S. Karger AG, Basel.)

Introduction: Frequent premature ventricular contractions (PVCs) can cause cardiomyopathy (CM). Postextrasystolic potentiation (PESP) and irregularity have been in implicated as triggers of PVC-CM. Because both phenomena can also be found in premature atrial contractions (PACs), it is speculated that frequent PACs have similar consequences., Methods and Results: A single-center, retrospective study included all consecutive patients undergoing a 14-day Holter monitors (November 2014 to October 2016). Patients were divided into four groups by ectopy burden group 1 (<1%) and remaining by tertiles (group 2-4). Echocardiographic and arrhythmic data were compared between PAC and PVC burdens. In addition, a translational PAC animal model was used to assess the chronic effects of frequent PACs. A total 846 patients were reviewed. In contrast to PVCs, we found no difference in left ventricular ejection fraction (LVEF), end-systolic and end-diastolic dimensions and presence of CM (LVEF <50%) between different PAC groups. Multivariate regression analysis demonstrated that only PVC burden predicted low EF (odds ratio, 1.1; confidence interval, 1.03-1.13; P = .001). While there was a weak correlation between PAC burden and supraventricular tachycardia (SVT) episodes and atrial fibrillation (AF) burden (r = 0.19; P < .001), there was no correlation between PAC burden and LVEF or CM. Finally, atrial bigeminy in our animal model did not significantly decrease LVEF after 3 months., Conclusion: PAC burden is associated with increased AF and SVT episodes. In contrast to a high PVC burden, a high PAC burden is not associated with CM. Our findings suggest that heart rate irregularity and/or PESP may play a minimal role in the pathophysiology of PVC-CM., (Published 2019. This article is a U.S. Government work and is in the public domain in the USA.)

Background: Maintenance of sinus rhythm after pulmonary vein isolation (PVI) for atrial fibrillation (AF) is associated with left atrial (LA) and ventricular (LV) reverse remodeling, although the degree varies among individuals. We hypothesized that frequent premature atrial complex (PAC) after PVI may attenuate the left heart reverse remodeling benefited from maintenance of sinus rhythm., Methods: We included 82 AF patients who underwent first-time PVI and 24-h Holter recordings at 6 months after PVI. All patients had no AF recurrence before this time. The number of PAC was categorized into tertiles: <90, 90-488 and >488 PACs/day. All patients underwent two-dimensional echocardiography and serum plasma B-type natriuretic peptide (BNP) measurement before and 6 months after PVI. LA reverse remodeling was defined as ≥15% decrease in LA volume index., Results: There was no significant difference in the baseline characteristics among the PAC tertiles except for sex. Six months after PVI, LA volume index, LV mass index, and serum BNP levels were significantly decreased in lower and middle PAC tertiles (all P < .05), whereas no significant changes were observed in upper PAC tertile. Frequency of LA reverse remodeling was significantly lower in upper tertile of PAC compared with middle and lower tertiles (22.2%, 57.1%, and 59.3%, P < .001). Baseline LA volume index, changes in LV mass index, and the frequency of PAC were independently associated with LA reverse remodeling (all P < .05)., Conclusions: Frequent PAC after PVI was associated with less left heart reverse remodeling in AF patients even without AF recurrence., (© 2019 Wiley Periodicals, Inc.)

Aims: Premature atrial contractions (PACs) are known to trigger and predict atrial fibrillation (AF). We sought to identify the determinants of PACs and the degree to which PACs mediate the effects of established risk factors for AF., Methods and Results: Predictors of baseline PAC frequency were examined using a Holter Study among 1392 participants in the Cardiovascular Health Study, a community-based cohort of individuals aged ≥65 years. Participants were then followed for their first diagnosis of AF. Independent predictors of PACs were identified, and the extent to which PACs might mediate the relationship between those predictors and AF was determined. The median hourly frequency of PACs was 2.7 (interquartile range 0.8-12.1). After multivariable adjustment, increasing age, increasing height, decreasing body mass index, and a history of myocardial infarction were each associated with more PACs. Regarding modifiable predictors, participants using beta-blockers had 21% less [95% confidence interval (95% CI) 9-30%, P = 0.001] and those performing at least moderate intensity exercise vs. lower intensity exercisers had 10% less (95% CI 1-18%, P = 0.03) PACs. Higher PAC frequency explained 34% (95% CI 22-57%, P < 0.0001) of the relationship between increasing age and AF risk and 27% (95% CI 10-75%, P = 0.004) of the relationship between taller height and AF risk., Conclusion: Enhancing physical activity and use of beta-blockers may represent fruitful strategies to mitigate PAC frequency. A substantial proportion of the excess risk of AF due to increasing age and taller height may be explained by an increase in PAC frequency., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Aims: QT interval may be considered an indirect marker of atrial repolarization. Aim of our study was to verify if QT interval variations precede the onset of atrial fibrillation (AF)., Methods: We analyzed 21 AF onsets recorded at 24-h Holter ECG. Triggering supraventricular extrabeats (TSVEB) were identified and matched to nontriggering supraventricular extrabeats (NTSVEB) with the same prematurity index. QT and QTc intervals and their variability (max-min QT interval) were measured in the 10 beats preceding TSVEB and NTSVEB., Results: QTc (470.1 ± 56.7 vs. 436.7 ± 25.6 ms; P = 0.006), QT (36.8 ± 13.1 vs. 21.1 ± 10.1 ms; P = 0.001) and QTc variability (41.5 ± 15.8 vs. 23.1 ± 11.9; P = 0.001) significantly varied between TSVEB and NTSVEB. By stratifying AF onsets in vagal (n = 10) and adrenergic (n = 11) according to Heart Rate Variability, significant differences emerged concerning QT (35.20 ± 16.48 vs. 22.70 ± 10.23 ms, P = 0.006) and QTc variability (39.30 ± 18.32 vs. 25.60 ± 12.91 ms, P = 0.029) for vagal onsets and QTc (477.73 ± 57.50 vs. 438.00 ± 28.55 ms, P = 0.045), QT (38.36 ± 9.79 vs. 19.73 ± 10.21 ms, P = 0.005) and QTc variability (43.55 ± 13.72 vs. 20.82 ± 11.01 ms, P = 0.004) for adrenergic onsets. By stratifying AF onsets in type I (n = 7) or II (n = 14) according to a cycle length variation in the 30 s before the onset greater or smaller than 10% respectively, significant differences were noted concerning QTc (477.73 ± 57.50 vs. 438 ± 28.55 ms, P = 0.045), QT (43.55 ± 13.72 vs. 20.82 ± 11.01 ms, P = 0.005) and QTc variability (43.55 ± 13.72 vs. 20.82 ± 11.01 ms, P = 0.004) in type I and QT (35.20 ± 16.48 vs. 22.70 ± 10.23 ms, P = 0.006) and QTc variability (39.30 ± 18.32 vs. 25.60 ± 12.91 ms, P = 0.029) in type II onsets., Conclusion: Prolongation and QT variability represent a relevant substrate marker in the genesis of AF, independently of the trigger type.

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., (Copyright © 2018. Published by Elsevier Inc.)

Background: Frequent 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., Methods: We 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., Results: Twelve 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, I 2  = 90.6%)., Conclusion: Frequent 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., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Atrial fibrillation (AF) is associated with increased morbidity and mortality. We sought to determine whether atrial premature complexes (APCs) detected during a standard exercise stress test (EST) in patients undergoing cardiac rehabilitation (CR) are associated with an increased risk of AF. The present study population comprised 6,523 consecutive patients without prior AF who participated in a CR program in a tertiary medical center in years 2009 to 2016. Multivariate analysis was used to identify the association between APCs during the baseline EST at CR and the risk for the development of AF over a mean follow-up period of 2.5 years. A total of 213 (3.7%) patients had APCs during their EST. Despite being older (mean age 63 ± 13 years old vs 58 ± 13; p <0.001, respectively), no other statistically significant differences were documented. Kaplan-Meier survival analysis showed that the rate of AF development during follow-up was significantly higher in patients with APCs at baseline EST (11%) as compared with those without APCs (5%; log-rank p <0.001 for the overall difference during follow-up). Consistently, multivariate analysis showed that patients with APCs showed >twofold increase risk for AF compared with those without APCs (hazard ratio 2.1; 95% confidence interval 1.36 to 3.25; p <0.001). In conclusion, our findings suggest that APCs detected during EST in patients participating in the CR program independently predict AF and can be used to improve risk stratification in this population., (Copyright © 2018. Published by Elsevier Inc.)

Atrial premature complexes (APCs) serve as acute triggers for atrial fibrillation (AF), but it is currently unknown whether the association between APCs and AF varies by race or sex. We examined the association between APCs and AF in 13,840 (mean age = 63 ± 8.4 years; 56% women; 37% black) participants from the REasons for Geographic And Racial Differences in Stroke study. APCs were detected on baseline electrocardiograms (2003 to 2007). Incident AF was identified by study-scheduled electrocardiograms and self-reported history at a follow-up examination. Logistic regression was used to compute odds ratios (OR) and 95% confidence intervals for the association between APCs and incident AF. A total of 950 participants (6.9%) had APCs at the baseline visit. After a median follow-up of 9.4 years, 1015 incident AF cases (7.3%) were detected. APCs were associated with an increased risk of AF (odds ratios = 1.92, 95% confidence intervals = 1.57, 2.35). The relation between APCs and AF did not vary by race (interaction p value = 0.56) or sex (interaction p value = 0.66). In conclusion, APCs detected on a routine electrocardiogram are associated with an increased risk of AF development, and this association does not vary by race or sex. The findings of this analysis suggest that the risk of AF associated with atrial ectopy does not account for the differential risk of AF that is observed in whites compared with blacks, and in men compared with women., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: The purpose of this study was to characterize the repeatability of ectopic beats, defined by premature atrial contractions (PACs) and premature ventricular contractions (PVCs), on ambulatory electrocardiogram (aECG) monitoring and evaluate the effect of length of aECG monitoring on the repeatability estimates., Methods: This analysis includes 95 randomly selected participants from the Atherosclerosis Risk in Communities Study (ARIC; 2011-2013). The participants wore a Holter monitor for two, 48-hr periods separated by a mean of 38 days following an identical, standardized protocol. We divided each 48-hr recording into 3-, 6-, 12-, and 24-hr recording periods and calculated intraclass correlation coefficients (ICCs) for PACs and PVCs and also as a percentage of the corresponding total of recorded beats per hour among these periods., Results: All participants had ≥1 PAC during the 48-hr recordings, and only two participants had no PVCs. ICCs were >0.83 for all indices and recording lengths ≥12 hrs. ICCs were intermediate for 6-hr recordings (range 0.80-0.83) and lower for 3-hr recordings (range 0.74-0.80). The ratio of the between- to within-participant variation increased with recording length., Conclusion: Repeatability of PACs and PVCs was excellent for recording lengths of 6-24 hr and fair for 3 hr. Repeatability varies over shorter duration recordings within the 48-hr recording period, and thus the present results have implications for detection algorithms for ectopic beats and can facilitate epidemiologic and clinical applications in which knowledge of measurement variability and misclassification are needed., (© 2017 Wiley Periodicals, Inc.)

Background: Our aim was to investigate the association of premature atrial complexes and the risk of recurrent stroke or death in patients with ischemic stroke in sinus rhythm., Methods: In a prospective cohort study, we used 24-hour Holter recordings to evaluate premature atrial complexes in patients consecutively admitted with ischemic strokes. Excessive premature atrial complexes were defined as >14 premature atrial complexes per hour and 3 or more runs of premature atrial complexes per 24 hours. During follow-up, 48-hour Holter recordings were performed after 6 and 12 months. Among patients in sinus rhythm, the association of excessive premature atrial complexes and the primary end point of recurrent stroke or death were estimated in both crude and adjusted Cox proportional hazards models. We further evaluated excessive premature atrial complexes contra atrial fibrillation in relation to the primary end point., Results: Of the 256 patients included, 89 had atrial fibrillation. Of the patients in sinus rhythm (n = 167), 31 had excessive premature atrial complexes. During a median follow-up of 32 months, 50 patients (30% of patients in sinus rhythm) had recurrent strokes (n = 20) or died (n = 30). In both crude and adjusted models, excessive premature atrial complexes were associated with the primary end point, but not with newly diagnosed atrial fibrillation. Compared with patients in atrial fibrillation, those with excessive premature atrial complexes had similarly high risks of the primary end point., Conclusions: In patients with ischemic stroke and sinus rhythm, excessive premature atrial complexes were associated with a higher risk of recurrent stroke or death., (Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Background: Autonomic dysfunction contributes to atrial fibrillation (AF)., Objective: We hypothesized that polysomnogram (PSG)-based heart rate variability (HRV) autonomic function biomarkers are associated with incident AF and these associations are modified by measures of sleep disordered breathing (SDB)., Methods: 2350 participants of a multi-center prospective study (Outcomes of Sleep Disorders in Older Men Study) without baseline AF underwent sleep studies with incident adjudicated AF follow up (8.0 ± 2.6 years). Cox proportional hazard models were used to analyze sleep study-ECG spectral HRV indices [low and high frequency power (LF, HF), LF/HF] and time domain indices [mean of normal to normal beats (MNN), short and long term variability (STV, LTV) and STV/LTV] and premature atrial contractions (PACs) and incident AF (HR and 95% CI). Statistical interactions between HRV and SDB were examined. Models were adjusted for age, race, body mass index, waist circumference, cardiac medications, co-morbid diseases, alcohol use and study site., Results: Lower LF/HF and lower LF were associated with higher AF incidence (LF/HF Q1 vs. Q4: 1.46, 1.02-2.08, LF Q1 vs. Q4: 1.46, 1.02-2.10). Higher STV/LTV was associated with an increased risk of AF (p-trend= 0.028). The highest PAC quartile had a 3-fold increased AF risk (2.99, 1.94-4.62) compared to the lowest quartile. A significant interaction of obstructive apnea was observed in the LF-AF relationship (0.045)., Conclusions: Sleep-related reduced sympathovagal balance (LF/HF) and increased atrial ectopy are independently associated with future AF; a relationship modified by obstructive apnea.

Background and Purpose: Stroke is independently associated with the common conditions of hypokalemia and supraventricular ectopy, and we hypothesize that the combination of excessive supraventricular ectopic activity and hypokalemia has a synergistic impact on the prognosis in terms of stroke in the general population., Methods: Subjects (55-75 years old) from the Copenhagen Holter Study cohort (N=671) with no history of atrial fibrillation or stroke were studied-including baseline values of potassium and ambulatory 48-hour Holter monitoring. Excessive supraventricular ectopic activity is defined as ≥30 premature atrial complexes per hour or any episodes of runs of ≥20. Hypokalemia was defined as plasma-potassium ≤3.6 mmol/L. The primary end point was ischemic stroke. Cox models were used., Results: Hypokalemia was mild (mean, 3.4 mmol/L; range, 2.7-3.6). Hypokalemic subjects were older (67.0±6.94 versus 64.0±6.66 years; P <0.0001) and more hypertensive (165.1±26.1 versus 154.6±23.5 mm Hg; P <0.0001). Median follow-up time was 14.4 years (Q1-Q3, 9.4-14.7 years). The incidence of stroke was significantly higher in the hypokalemic group (hazard ratio, 1.84; 95% confidence interval, 1.04-3.28) after covariate adjustments, as well as in a competing risk analysis with death (hazard ratio, 1.51; 95% confidence interval, 1.12-2.04). Excessive supraventricular ectopic activity was also associated with stroke (hazard ratio, 2.23; 95% confidence interval, 1.33-3.76). The combination of hypokalemia and excessive supraventricular ectopic activity increased the risk of events synergistically. Stroke rate was 93 per 1000 patient-year ( P <0.0001) in this group (n=17) compared with 6.9 (n=480); 11 (n=81), and 13 (n=93) per 1000 patient-year in the groups without the combination., Conclusions: The combination of hypokalemia and excessive supraventricular ectopy carries a poor prognosis in terms of stroke., (© 2017 American Heart Association, Inc.)

Background and Objective: Recent randomized studies have shown the potential of prolonged cardiac rhythm monitoring to detect silent paroxysmal atrial fibrillation (PAF) in patients with cryptogenic stroke. Our aim was to identify clinical and magnetic resonance imaging (MRI) factors that predict the detection of PAF during long-duration rhythm cardiac Holter (LDRCH) monitoring., Methods: A retrospective analysis was performed using data from 171 patients with cryptogenic stroke or transient ischemic attack who underwent LDRCH monitoring (i.e., 21 days) from 2009 to 2013. Clinical, echocardiographic, and imaging predictors of atrial fibrillation (AF) were determined by multivariable analysis., Results: PAF lasting more than or equal to 30 seconds was diagnosed in 26 of 171 (15%) patients. Median delay to first detected AF episode was 7 (interquartile range: 2-13) days. Four factors were independently predictive of PAF detection on LDRCH: age more than 70 years (odds ratio [OR], 4.6; 95% confidence interval [CI], 1.5-13.8); premature atrial complex on electrocardiogram (OR, 4.6; 95% CI, 1.1-19.6); left ventricular hypertrophy on transthoracic echocardiography (OR, 6.4, 95% CI, 1.6-26.4); and previous white matter lesions on brain MRI (OR, 4.2; 95% CI, 1.2-15.6). Recent brain infarction pattern on diffusion-weighted imaging was not associated with PAF detection on LDRCH., Conclusion: LDRCH is a noninvasive and inexpensive test with a high rate of AF detection in patients with cryptogenic stroke or transient ischemic attack. Occult PAF was more commonly diagnosed in older patients with premature atrial complex on the baseline electrocardiogram, left ventricular hypertrophy on echocardiography, and with previous white matter lesions on brain MRI., (Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Aims: The aim of the study was to assess a possible circadian variation of premature atrial contractions (PACs) in a community-based population and to determine if the daily variation could be used to assess a more vulnerable period of PACs in predicting later incidence of atrial fibrillation (AF)., Methods and Results: We studied 638 subjects between the ages of 55 and 75 years from the Copenhagen Holter Study who underwent up to 48 h electrocardiogram recording. Follow-up on cardiovascular endpoints was performed in 2013 with a median follow-up time of 14.4 years. According to previous studies, two subgroups were studied based on a cut-off point of ≥720 PACs/day termed frequent PACs (n = 66) and not frequent PACs with <720 PACs/day (n = 572). Based on median values, a circadian rhythm could not be demonstrated in the population as a whole and the group without frequent PACs. However, a circadian variation was observed in the group with frequent PACs, who had the fewest PACs/h during the night with a nadir at 6 am and then reaching a peak value in the afternoon at 3 pm. Runs of PACs in all subjects showed a similar circadian variation. Both PACs/h and runs of PACs seemed to follow the daily variation in heart rate. After adjusting for relevant risk factors, the risk of AF was equal in all time intervals throughout the day., Conclusion: Premature atrial contractions showed a circadian variation in subjects with frequent PACs. No specific time interval of the day was more predictive of AF than others., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.)

Atrial fibrillation (AF) is associated with the autonomic nervous system (ANS), and fluctuation of autonomic tone is more prominent in patients with AF. As autonomic tone affects the heart rate (HR), and there is an inverse relationship between HR and PR interval, PR interval variation could be greater in patients with AF than in those without AF. The purpose of this study was to investigate the correlation between PR interval variation and new-onset AF in patients with frequent PACs.We retrospectively enrolled 207 patients with frequent PACs who underwent electrocardiographs at least 4 times during the follow-up period. The PR variation was calculated by subtracting the minimum PR interval from the maximum PR interval. The outcomes were new occurrence of AF and all-cause mortality during the follow-up period.During a median follow-up of 8.3 years, 24 patients (11.6%) developed new-onset AF. Univariate analysis showed that prolonged PR interval (PR interval > 200 ms, P = 0.021), long PR variation (PR variation > 36.5 ms, P = 0.018), and PR variation (P = 0.004) as a continuous variable were associated with an increased risk of AF. Cox regression analysis showed that prolonged PR interval (hazard ratio = 3.321, 95% CI 1.064-10.362, P = 0.039) and PR variation (hazard ratio = 1.013, 95% CI 1.002-1.024, P = 0.022) were independent predictors for new-onset AF. However, PR variation and prolonged PR interval were not associated with all-cause mortality (P = 0.465 and 0.774, respectively).PR interval variation and prolonged PR interval are independent risk factors for new-onset AF in patients with frequent PACs. However we were unable to determine a cut-off value of PR interval variation for new-onset AF., Competing Interests: The authors have no funding and conflicts of interest to disclose.

The clinical significance of prolonged PR interval has not been evaluated in patients with frequent premature atrial contractions (PACs). We investigated whether prolonged PR interval could predict new occurrence of atrial fibrillation (AF) in patients with frequent PACs. We retrospectively analyzed 684 patients with frequent PACs (> 100 PACs/day) who performed repeated 24-hour Holter monitoring. Prolonged PR interval was defined as longer than 200 msec. Among 684 patients, 626 patients had normal PR intervals (group A) and 58 patients had prolonged PR intervals (group B). After a mean follow-up of 59.3 months, 14 patients (24.1%) in group B developed AF compared to 50 patients (8.0%) in group A (P < 0.001). Cox regression analysis showed that prolonged PR interval (hazard ratio [HR], 1.950; 95% CI, 1.029-3.698; P = 0.041), age (HR, 1.033; 95% CI, 1.006-1.060; P = 0.015), and left atrial (LA) dimension (HR, 1.061; 95% CI, 1.012-1.112; P = 0.015) were associated with AF occurrence. Prolonged PR interval, advanced age, and enlarged LA dimension are independent risk factors of AF occurrence in patients with frequent PACs.

Background: The relevance of focal triggers in persistent atrial fibrillation (PerAF) and long-standing persistent atrial fibrillation (LSPAF) has not been previously investigated., Objective: We prospectively evaluated the prevalence and distribution of AF triggers in patients referred for catheter ablation of PerAF and LSPAF., Methods: We analyzed consecutive patients undergoing first time AF ablation who underwent a standardized trigger protocol including cardioversion of induced or spontaneous AF and infusion of up to 20 μg of isoproterenol for 15-20 minutes either before or after pulmonary vein (PV) isolation accomplished. Triggers were defined as AF/sustained atrial tachyarrhythmia or repetitive atrial premature depolarizations., Results: A total of 2168 patients were included (mean age 57 ± 11 years; 1636 [75%] men), with 1531 patients having paroxysmal AF (PAF) (71%), 496 having PerAF (23%), and 141 having LSPAF (7%). PV triggers were found in 1398 patients with PAF (91%), 449 patients with PerAF (91%), and 129 patients with LSPAF (91%) (P = .856 for comparison across groups). Non-PV triggers were elicited in a total of 234 patients (11%), and the prevalence was similar across the different types of AF (PAF, 165 [11%]; PerAF, 54 [11%]; LSPAF, 15 [11%]; P = .996 for comparison across groups)., Conclusion: PVs are the main AF trigger site in patients with PerAF and LSPAF, with an overall prevalence similar to that found in patients with PAF. These results support the current recommendations for PV isolation as the cornerstone of catheter ablation to eliminate AF triggers in PerAF and LSPAF., (Copyright © 2016 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Identification of precursors of atrial fibrillation (AF) may lead to early detection and prevent associated morbidity and mortality. This study aimed to examine the association between frequent atrial premature complexes (APCs) and incidence of AF. For this retrospective cohort study, we analyzed Holter recordings obtained from 2000 to 2010 of 1,357 veterans free of AF at baseline. All pertinent data in electronic medical records were reviewed to ascertain baseline characteristics. Holter groups with frequent (≥100/day) and infrequent (<100/day) APCs were compared for development of new AF over a median follow-up of 7.5 years. Multivariate Cox regression analyses were performed before and after propensity score matching. Mean age was 64 years with 93% men. Mean body mass index, hemoglobin A1C, low-density lipoprotein, left atrial size, and heart rate were 31.24 kg/m(2), 6.42%, 107.92 mg/dl, 4.26 cm, and 73 beats/min, respectively. AF was noted in 21.8% of patients with frequent APCs compared to 5.6% of those with infrequent APCs. After adjusting for demographics, medication use, co-morbidities, and laboratory and echocardiographic findings, multivariate Cox regression analyses confirmed frequent APCs to be independently associated with higher incidence of AF (hazard ratio [HR] 2.97, 95% confidence interval [CI] 1.85 to 4.80; p <0.001). In propensity-matched groups, this association remained significant (HR 2.87, 95% CI 1.65 to 4.98; p <0.001). Additionally, atrial couplets (≥50/day), atrial bigeminy (≥50/day), frequent runs of ≥3 APCs (≥20 runs/day), and longer runs (≥10 beats/run) were significantly associated with AF (HR 3.11, 3.67, 2.94, and 1.73, respectively, all p <0.05). In conclusion, frequent APCs (≥100/day) are associated with greater risk of AF., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Introduction: Patients with paroxysmal atrial fibrillation (AF) often transition between sinus rhythm and AF. For AF to initiate there must be both a trigger and a substrate that facilitates reentrant activity. This trigger is often caused by a premature atrial contraction or focal activations within the atrium. We hypothesize that specific architectures of fibrosis alter local conduction to enable AF., Methods and Results: Control goats (n = 13) and goats in chronic AF (for an average of 6 months, n = 6) had a high-density electrode plaque placed on the LA appendage. Conduction patterns following a premature atrial contraction, caused by an electrical stimulation, were quantified to determine regions of conduction slowing. These regions were compared to architecture, either diffuse fibrosis or regions of obstructive fibrosis, and overall fibrosis levels as determined by histology from the mapped region. The chronic AF goats had more obstructive fibrosis than the controls (17.5 ± 8.0 fibers/mm(2) vs. 8.6 ± 3.0 fibers/mm(2)). Conduction velocity of the AF goats was significantly slowed compared to the control goats in the transverse direction (0.40 ± 0.04 m/s vs. 0.53 ± 0.15 m/s) but not in the longitudinal direction (0.70 ± 0.27 m/s vs. 0.76 ± 0.18 m/s)., Conclusions: AF-induced atrial remodeling leads to increased obstructive fibrosis and conduction velocity slowing transverse to fiber orientation following premature stimuli. The decrease in conduction velocity causes a decrease in the cardiac wavelength, and increases the likelihood of reentry and AF onset., (© 2015 Wiley Periodicals, Inc.)

Background: Atrial fibrillation (AF) episodes are thought to be started by an electrical trigger reaching susceptible atria. Such a trigger could be present long before the occurrence of sustained symptomatic arrhythmia., Objective: We sought to determine whether supraventricular extrasystoles (SVESs) and supraventricular tachycardias (SVTs) measured at 24-hour Holter electrocardiogram were associated with an increased incidence of AF., Methods: In 1998-2000, 389 individuals (44% men; mean age 65 years) were examined using 24-hour Holter electrocardiogram. Six individuals with known prevalent AF were excluded. After a mean follow-up of 10.3 years, there were 45 cases of incident AF. Hazard ratios (HRs) were computed using multivariable Cox regression adjusting for age, sex, systolic blood pressure, height, weight, smoking, and homeostatic model assessment of insulin resistance., Results: Frequency of SVESs as well as SVT episodes per hour were independent predictors of incident AF (HR per log unit 1.38; 95% confidence interval 1.14-1.68; P = .001 and HR 1.95; 95% confidence interval 1.21-3.13; P = .006, respectively). Further adjustment for education level, alcohol use, use of medication, and physical activity did not substantially alter the results, nor did analysis using competing risks regression accounting for a competing risk of death. The maximum duration of SVT or the heart rate at SVT was not significantly associated with the incidence of AF., Conclusion: SVESs and SVTs independently predict AF. The prognostic significance was similar for SVESs, SVTs, and a combination of the two. Repeated efforts to detect AF could be of merit in individuals with frequent supraventricular activity., (Copyright © 2015 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: The study of atrial conduction defects associated with the onset of paroxysmal atrial fibrillation (PAF) can be addressed by analyzing the P wave from the surface electrocardiogram (ECG). Traditionally, signal-averaged ECGs have been mostly used for this purpose. However, this alternative hinders the possibility to quantify every single P wave, its variability over time, as well as to obtain complimentary and evolving information about the arrhythmia. This work analyzes the time progression of several time and frequency P wave features as potential indicators of atrial conduction variability several hours preceding the onset of PAF., Methods: The longest sinus rhythm interval from 24-hour Holter recordings of 46 PAF patients was selected. Next, the 2 hours before the onset of PAF were extracted and divided into two 1-hour periods. Every single P wave was automatically delineated and characterized by 16 time and frequency metrics, such as its duration, absolute energy in several frequency bands and high-to-low-frequency energy ratios. Finally, the P wave variability over each 1-hour period was estimated from the 16 features making use of a least-squares linear fitting. As a reference, the same parameters were also estimated from a set of 1-hour ECG segments randomly chosen from a control group of 53 healthy subjects age-, gender-, and heart rate-matched., Results: All the analyzed metrics provided an increasing P wave variability trend as the onset of PAF approximated, being P wave duration and P wave high-frequency energy the most significant individual metrics. The linear fitting slope α associated with P wave duration was (2.48 ± 1.98)×10(-2) for healthy subjects, (23.8 ± 14.1)×10(-2) for ECG segments far from PAF and for (81.8 ± 48.7)×10(-2) ECG segments close to PAF p = 6.96×10(-22) . Similarly, the P wave high-frequency energy linear fitting slope was (2.42 ± 4.97)×10(-9) , (54.2 ± 107.1)×10(-9) and (274.2 ± 566.1)×10(-9) , respectively (p = 2.85×10(-20) ). A univariate discriminant analysis provided that both P wave duration and P wave high-frequency energy could discern among the three ECG sets with diagnostic ability around 80%, which was improved up to 88% by combining these metrics in a multivariate discriminant analysis., Conclusion: Alterations in atrial conduction can be successfully quantified several hours before the onset of PAF by estimating variability over time of several time and frequency P wave features., (© 2014 Wiley Periodicals, Inc.)