Rhythm Status Research Articles

The effects of dynamic daylight-like light on the rhythm, cognition, and mood of irregular shift workers in closed environment

Shift workers are mostly suffered from the disruption of circadian rhythm and health problems. In this study, we designed proper light environment to maintain stable circadian rhythm, cognitive performance, and mood status of shift workers. We used five-channel light-emitting diodes to build up the dynamic daylight-like light environment. The illuminance, correlated color temperature, and circadian action factor of light were tunable in the ranges of 226 to 678 lx, 2680 to 7314 K, and 0.32 to 0.96 throughout the day (5:30 to 19:40). During the nighttime, these parameters maintained about 200 lx, 2700 K, and 0.32, respectively. In this light environment, three subjects had engaged in shift work for 38 consecutive days. We measured plasma melatonin, activity counts, continuous performance tests, and visual analogue scale on mood to assess the rhythm, cognitive performance, and mood of subjects. After 38-day shift work, the subjects’ peak melatonin concentration increased significantly. Their physiological and behavioral rhythms maintained stable. Their cognitive performance improved significantly after night work, compared with that before night work. Their mood status had no significant change during the 38-day shift work. These results indicated that the light environment was beneficial to maintain circadian rhythm, cognitive performance and mood status during long-term shift work in closed environment.

Electrical cardioversion to assess the association between self-reported symptoms and rhythm status in patients with persistent atrial fibrillation

Abstract Funding Acknowledgements Type of funding sources: None. Background. Knowledge about the association between symptoms and rhythm status (symptom-rhythm correlation) has potential clinical implications as it may identify patients with atrial fibrillation (AF) who profit from rhythm control in regard to reduction in symptom burden and improvement in quality of life. However, standardized strategies to assess symptom-rhythm correlation in AF patients are currently not available. Purpose. This study aimed to assess symptom-rhythm correlation in patients with persistent AF using electrical cardioversion (ECV) as a diagnostic probe. Methods. We used ECV to examine symptom-rhythm correlation in 81 patients with persistent AF. The presence of self-reported symptoms before ECV and at the first outpatient AF clinic follow-up visit (within 1-month) was assessed to determine the prevalence of a symptom-rhythm correlation (defined as self-reported symptoms present during AF and absent in sinus rhythm or absent in AF and yet relief during sinus rhythm). The symptom-rhythm correlation was absent in patients with symptoms before ECV who remained symptomatic during sinus or in patients with symptoms prior to ECV and without symptoms in AF after ECV. Asymptomatic patients before ECV with or without symptoms in AF or sinus rhythm afterwards had no symptom-rhythm correlation as well. The symptom-rhythm correlation was unevaluable in patients who were symptomatic in AF before ECV and at the first outpatient AF clinic follow-up visit. In addition, predominant self-reported symptoms (symptoms with highest self-reported symptom burden) were assessed to evaluate the symptom patterns around ECV. Intra-individually variable symptom patterns were defined as changes in predominant self-reported symptoms within patients around ECV. Results. Symptom-rhythm correlation was assessed in all patients. Only in 18 patients (22%), a symptom-rhythm correlation could be documented. Twenty-eight patients (35%) did not show any symptom-rhythm correlation and 35 patients (43%) had an unevaluable symptom-rhythm correlation as these patients were in symptomatic AF both at baseline and at the first outpatient AF clinic follow-up visit. Importantly, self-reported symptom patterns around ECV were intra-individually variable in 10 patients (12%) without symptom-rhythm correlation (of which 9 patients (11%) had AF recurrence) and in 2 patients (2%) with an unevaluable symptom-rhythm correlation. Conclusions. In patients with persistent AF, the prevalence of a symptom-rhythm correlation around ECV is low, but ECV often changes symptom pattern. Further studies are warranted to identify more optimal strategies to assess symptom-rhythm correlation in patients with persistent AF. Abstract Figure. Symptom-rhythm correlation and patterns

Increased beat-to-beat variability of cerebral microcirculatory perfusion during atrial fibrillation: a near-infrared spectroscopy study.

Atrial fibrillation (AFib) is associated with cognitive decline/dementia, independently from clinical strokes or transient ischaemic attacks (TIA). Recent in silico data suggested that AFib may induce transient critical haemodynamic events in the cerebral microcirculation. The aim of this study is to use non-invasive spatially resolved cerebral near-infrared spectroscopy (SRS-NIRS) to investigate in vivo beat-to-beat microcirculatory perfusion during AFib and after sinus rhythm (SR) restoration. Cerebral SRS-NIRS with high-frequency sampling (20 Hz) and non-invasive systemic haemodynamic monitoring were recorded before and after elective electrical cardioversion (ECV) for AFib or atrial flutter (AFL). To assess beat-to-beat effects of the rhythm status, the frequency distribution of inter-beat differences in tissue haemoglobin index (THI), a proxy of microcirculatory cerebral perfusion, was compared before and after SR restoration. Fifty-three AFib/AFL patients (mean age 69 ± 8 years, 79% males) were ultimately enrolled. Cardioversion was successful in restoring SR in 51 (96%) patients. In front of a non-significant decrease in arterial blood pressure extreme events between pre- and post-ECV measurements, a significant decrease of both hypoperfusive and hyperperfusive/hypertensive microcirculatory events was observed after SR restoration (P < 0.001 and P = 0.041, respectively). The present is the first in vivo demonstration that SR restoration by ECV significantly reduces the burden of extreme single-beat haemodynamic events in cerebral microcirculation. Future studies are needed to assess whether SR maintenance might slow long-term AFib-correlated cognitive decline/dementia.

Beyond Extracorporeal Cardiopulmonary Resuscitation: Systems of Care Supporting Cardiac Arrest Patients

Introduction: Out-of-hospital cardiac arrest (OHCA) is a major cause of death and disability in the United States. Cardiac arrest centers (CAC) are necessary for the management of these critically ill and complex post arrest patients due to their specialized services and provider expertise. We report the case of a patient with OHCA and the systems of care involved in his resuscitation and recovery. Case Report: Emergency medical services attended a 39-year-old male with ongoing bystander cardiopulmonary resuscitation (CPR) after a witnessed collapse. Despite receiving appropriate advanced cardiac life support, including three defibrillations, he remained in refractory ventricular fibrillation. A prehospital physician identified him as an extracorporeal cardiopulmonary resuscitation (ECPR) candidate due to his age, witnessed arrest, refractory rhythm, and functional status. He was expedited to a CAC but no longer qualified for ECPR due to the time limit. He was resuscitated by the multiple teams activated prior to his arrival. He eventually had sustained return of circulation, was taken to the catheterization lab for emergent percutaneous coronary intervention, and recovered with a good neurologic outcome. Conclusion: Cardiac arrest centers may be capable of advanced interventions including ECPR. However, the systems of care offered by these centers is itself a lifesaving intervention. As this case highlights, despite not receiving the specified intervention (ECPR) the systems of care required to offer such a resource led to this favorable outcome.

Circulating inflammatory markers may mediate the relationship between low carbohydrate diet and circadian rhythm in overweight and obese women

BackgroundLow carbohydrate diet (LCD) can improve inflammation and obesity and also circadian rhythm disorders can lead to increased inflammation in obese individuals. The purpose of this study is to evaluate the association between adherence of LCD and circadian rhythm mediated by inflammatory markers including transforming growth factor-β (TGF-β), interleukin-1β (IL-1β) and Galectin-3 in overweight and obese women.Methods304 women affected by overweight and obesity were enrolled. We evaluated LCD scores by Semi-quantitative food frequency questionnaire (FFQ) of 147 items. The morning-evening questionnaire (MEQ) was applied to evaluate the circadian rhythm. Biochemical parameters such as inflammatory markers and anthropometric components were assessed.ResultsThere was a negative significant correlation between adherence of LCD and circadian rhythm status. In other words, as the LCD scores increased, the odds of circadian rhythm disturbance in intermediate group and morning type persons decreased compared to evening type. It was showed that, IL-1β and Galectin-3 in intermediate and morning type groups, destroyed the significance of this relationship and may be considered as mediating markers.ConclusionAdherence of LCD can improve the circadian rhythm by reducing levels of inflammatory markers and may be considered as a treatment for obesity.

Factors Contributing to Exercise Intolerance in Patients With Atrial Fibrillation

Reduced exercise capacity and exercise intolerance are commonly reported by individuals with atrial fibrillation (AF). Our objectives were to evaluate the contributing factors to reduced exercise capacity and describe the association between subjective measures of exercise intolerance versus objective measures of exercise capacity. Two hundred and three (203) patients with non-permanent AF and preserved ejection fraction undergoing cardiopulmonary exercise testing (CPET) were recruited. Clinical characteristics, AF-symptom evaluation, and transthoracic echocardiography measures were collected. Peak oxygen consumption (VO2peak) was calculated during CPET as an objective measure of exercise capacity. We assessed the impact of 16 pre-defined clinical features, comorbidities and cardiac functional parameters on VO2peak. Across this cohort (Age 66±11 years, 40.4% female and 32% in AF), the mean VO2peak was 20.3±6.3 mL/kg/min. 24.9% of patients had a VO2peak considered low (<16 mL/kg/min). In multivariable analysis, echocardiography-derived estimates of elevated left ventricular (LV) filling pressure (E/E') and reduced chronotropic index were significantly associated with lower VO2peak. The presence of AF at the time of testing was not significantly associated with VO2peak but was associated with elevated minute ventilation to carbon dioxide production indicating impaired ventilatory efficiency. There was a poor association between VO2peak and subjectively reported exercise intolerance and exertional dyspnoea. Reduced exercise capacity in AF patients is associated with elevated LV filling pressure and reduced chronotropic response rather than rhythm status. Subjectively reported exercise intolerance is not a sensitive assessment of reduced exercise capacity. These findings have important implications for understanding reduced exercise capacity amongst AF patients and the approach to management in this cohort. (ACTRN12619001343190).

Biatrial ablation vs. Pulmonary vein isolation in atrial fibrillation patients undergoing cardiac surgery: a retrospective study

Objectives Surgical ablation is an established treatment for patients with atrial fibrillation undergoing cardiac surgery. This study aimed to compare postoperative rhythm outcomes and pacemaker implantation rates after biatrial ablation or pulmonary vein isolation (PVI) concomitantly with other cardiac surgery. Design: In a retrospective study, we included patients who underwent biatrial ablation or PVI. Postoperative rhythm status was assessed by Holter monitoring. All data on outcomes and patient characteristics were collected retrospectively. Results: In total 109 patients had a biatrial procedure whereas 337 had PVI performed. In patients with persistent/long-standing persistent atrial fibrillation, freedom from atrial fibrillation was more common after biatrial ablation than after PVI (63% and 45%, respectively; p = .039). Postoperative permanent pacemaker implantation was more common after biatrial ablation (12% and 6%, respectively; p = .039), compared to PVI. Age < 65 years (OR:2.0, 95% CI:1.1–3.6) was a predictor of freedom from atrial fibrillation in the biatrial group, whereas absence of left atrial dilatation (OR:1.8, 95% CI:1.1–3.2) and HAS-BLED score < 2 (OR:1.9, 95% CI:1.0–3.8) were significant predictors of freedom from atrial fibrillation in the PVI group. Conclusions: In patients with persistent/long-standing persistent atrial fibrillation, biatrial ablation is more effective than PVI in terms of obtaining freedom from postoperative atrial fibrillation. Although our groups were heterogenic in terms of concomitant surgery, our study also indicates that the risk of needing a permanent pacemaker is higher after biatrial ablation, compared to PVI. Therefore, our study highlights that the decision between biatrial ablation or PVI should be performed on an individual basis.

Detection of new-onset atrial fibrillation in heart failure patients using daily non-invasive ECG monitoring in the TIM-HF2 telemedicine trial

Abstract Background Heart failure (HF) and atrial fibrillation (AF) impair the prognosis when they occur concomitantly. Recent telemedical studies suggest that HF patients with AF may derive a greater benefit from telemedicine care but the results are inconsistent. The rate of newly detected AF in HF patients by daily non-invasive electrocardiogram (ECG) monitoring is unknown and a possible influence on the outcome of remote patient management (RPM) remains unclear. Purpose We aimed to investigate the detection of new atrial fibrillation in patients assigned to RPM in comparison to patients assigned to usual care (UC) in the TIM-HF2 trial. Methods The prospective, multicentre and controlled TIM-HF2 trial randomised 1538 patients (765 RPM, 773 UC). All patients had a 12-channel ECG at baseline and after one year at the final study visit. Patients who were assigned to RPM additionally transmitted a daily ECG to the telemedical centre (TMC). We excluded all patients with pacemaker including implantable cardioverter defibrillator (ICD) or cardiac resynchronisation therapy (CRT) in the baseline ECG, leaving 879 patients for analysis (RPM: 442 and UC: 437). The patients were stratified into patients with SR and patients with AF according to the rhythm documented at baseline. The primary endpoint of this analysis was newly documented AF within one year after randomisation. We analysed the daily to the telemedical centre transmitted ECGs of patients assigned to RPM with the documented rhythm status of the ECGs performed at the final study visit of patients assigned to UC. Results 569 patients had SR and 310 patients had AF at baseline. The proportion of patients with AF was nearly the same in the RPM (159, 36.0%) and the UC (151, 34.6%) group. 68 patients (24.0%) were detected with new atrial fibrillation in the RPM group compared to 22 patients (7.8%) in the UC trial arm during the one-year follow-up (p&amp;lt;0.001, number needed to screen 6). Conclusion In patients with heart failure and daily ECG transmission, atrial fibrillation was detected three times more frequently in comparison to usual care within one year. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): The TIM-HF2 study was supported by a research grant of the German Federal Ministry of Education and Research (grant numbers 13KQ0904A, 13KQ0904B, 13KQ1104A). The TIM-HF2 study was a part of the research and development project “Gesundheitsregion der Zukunft Nordbrandenburg – Fontane” (Fontane). The Fontane system was developed in private–public partnership (PPP) supported by research and development grants from the German Federal Ministry of Education and Research, the European Regional Development, and the Federal State Brandenburg.

Impact of electrical cardioversion on quality of life for patients with symptomatic persistent atrial fibrillation: Is there a treatment expectation effect?

We examined the effect of ECV and rhythm status on QoL of patients with symptomatic persistent AF in a randomized controlled trial. The elective cardioversion for prevention of symptomatic atrial fibrillation trial examined the efficacy of dronedarone around the time of ECV in maintaining SR. Quality of life was measured with the University of Toronto Atrial Fibrillation Severity Scale. The primary outcome was the change in AF symptom severity (∆AFSS) score over 6 months (0-35 points, with higher scores reflecting worse QoL and a minimal clinically important difference defined as ∆AFSS ≥3 points). Multivariable linear regression was performed to identify factors associated with changes in QoL. We included 148 patients with complete AFSS scores at baseline and 6 months. Over 6 months, QoL improved irrespective of rhythm status (ΔAFSS scores for patients who (i) maintained SR; (ii) had AF relapse after successful ECV; and (iii) had unsuccessful ECV were -6.8 ± 6.4 points, -4.1 ± 6.2 points, and -4.0 ± 5.8 points respectively, P < .01 for all subgroups). After adjustment of baseline covariates, maintenance of SR was associated with QoL improvement (ΔAFSS: -3.8 points, 95% CI: -6.0 to -1.6 points, P < .01). Maintenance of SR was associated with clinically relevant improvement in patients' QoL at 6 months. Patients with AF recurrence had a small but still relevant improvement in their QoL, potentially due to factors other than sinus rhythm.

Assessment of the Left Ventricular Diastolic Function and Its Association with the Left Atrial Pressure in Patients with Atrial Fibrillation.

Background and ObjectivesThe evaluation of left ventricular (LV) diastolic function in patients with atrial fibrillation (AF) is challenging. This study aimed to investigate the efficacy of the diagnostic algorithm for LV diastolic dysfunction (LVDD) in the current guidelines and to evaluate the association between increased left atrial pressure (LAP) and LV diastolic parameters.MethodsOne hundred and twenty-four patients with non-valvular AF and a preserved LV ejection fraction who had the same rhythm status on echocardiography and LAP measurements during catheter ablation were included. LV diastolic function was classified as normal, indeterminate, or LVDD according to the recent guidelines. Increased LAP was defined as mean LAP (mLAP) ≥15 mmHg.ResultsThe mLAP was not different among the normal, indeterminate, and LVDD groups. However, the prevalence of increased LAP was higher in the LVDD group. Among the LV diastolic parameters, only medial E/e′ was independently associated with mLAP in the whole study population. In patients with persistent AF (PeAF), E/e′ and e′ were significantly associated with mLAP, whereas in paroxysmal AF (PAF), mLAP was not associated with the LV diastolic parameters but with left atrial conduit function.ConclusionsIn general, increased LAP is known to be closely related with LVDD. However, the algorithm for LVDD from recent guidelines does not reflect well the increased LAP in AF patients. The diastolic parameters may aid in estimating the increased LAP in PeAF but may only have limited value for assessing increased LAP in PAF.

Electrocardiogram-based pulse prediction during cardiopulmonary resuscitation

ObjectiveResuscitation requires CPR interruptions every 2 min to assess rhythm and pulse status. We developed a method to predict real-time pulse status in organized rhythm ECG segments with and without CPR artifact. MethodsThe study cohort included patients who received attempted resuscitation following ventricular fibrillation arrest. Using audio-supplemented defibrillator recordings, we annotated CPR, rhythm, and pulse status at each two-minute rhythm/pulse check. Paired ECG segments with and without CPR were extracted at each rhythm/pulse check. Using one-third of cases for training and two-thirds for validation, we developed three wavelet-based ECG features and combined them with a logistic model to predict pulse status. Predictive performances of each individual ECG feature and the combined logistic model were measured by the area under the receiver operator characteristic curve (AUC) in the validation cases with and without CPR. ResultsThere were 238 cases and 911 ECG segment pairs. Among 319 organized rhythm segments in the validation set, AUC for pulse prediction during CPR ranged from 0.67 to 0.79 for the individual ECG features. The logistic model was more predictive than any individual feature (AUC 0.84, 95% CI 0.80–0.89, p < 0.05 for each comparison) and performed similarly regardless of CPR (p = 0.2 for difference). ConclusionECG features extracted by wavelet analysis predicted pulse status with moderate accuracy among organized rhythm segments with and without CPR. Further study is required to understand how real-time pulse prediction during CPR could help direct care while limiting CPR interruption.

Abstract 335: Predicting Pulse Status From the ECG Signal Without Interrupting CPR

Objective: Currently, cardiac arrest resuscitation requires interruptions in CPR every 2 minutes to assess cardiac rhythm and pulse. A method which analyzed the ECG during CPR to predict whether or not an organized rhythm generated a pulse could help to direct care and limit CPR interruptions. We evaluated a real-time method to predict pulse status from organized rhythm ECG segments with and without CPR. Methods: The study cohort received attempted resuscitation by a metropolitan EMS system following out-of-hospital ventricular fibrillation arrest. Two-minute rhythm/pulse checks on the continuous defibrillator recordings were annotated for CPR, rhythm, and pulse status using the ECG, impedance, and accelerometer signals, the audio recording, and EMS record. Pulse was defined by the presence of a palpable pulse by EMS. Paired ECG segments with and without CPR were extracted at each rhythm/pulse check. Using organized rhythm segments from one-third of cases for training, we developed four ECG features using wavelet analysis (median power values in three frequency bands and QRS rate) and a logistic model to predict pulse status. Predictive performances of each ECG feature and the logistic model were measured by AUC in the remaining validation cases with and without CPR. Results: There were 238 cases and 911 paired segments with a median of 3 (IQR 2,5) paired segments per case. Among 319 organized rhythm segments in the validation set, AUC for pulse prediction ranged from 0.67 to 0.79 for the individual ECG features (Figure). The logistic model was more predictive than any individual feature (AUC 0.84, 95% CI 0.80-0.89, p &lt; 0.05 for each comparison). The model predicted pulse similarly regardless of CPR activity (p = 0.2). Conclusion: ECG features extracted by wavelet analysis were predictive of pulse status among organized rhythm segments with and without ongoing CPR. Further study is required to understand how pulse prediction could guide rescuer actions in real-time.

P3106Atrial fibrillation is not associated with the responses to exercise training in heart failure patients with preserved ejection fraction

Abstract Background Atrial fibrillation (AF) is known as a common arrhythmia in heart failure patients with preserved left ventricular ejection fraction (HFpEF). Several studies have reported that HFpEF patients with AF show lower exercise tolerance and poorer prognosis as compared with those with sinus rhythm (SR). On the other hand, exercise training is documented to improve peripheral muscle function and exercise tolerance in HFpEF patients. However, the relationship between AF status and outcomes due to exercise training is still unclear in these patients. Purpose We aimed to investigate the influence of AF on the responses to outcomes with exercise training in HFpEF patients. Methods We studied 426 patients with HFpEF who received 5-month cardiac rehabilitation including exercise training during hospitalization and after hospital discharge. As clinical characteristics, we obtained body mass index, disease aetiology, comorbidity conditions, blood examination and echocardiographic variables from medical records. We also measured isometric quadriceps strength (QS) and 6-minute walk distance (6MWD) as peripheral muscle strength and exercise tolerance, respectively. The QS and 6MWD were assessed at hospital discharge as the baseline and 5 months later. AF status was determined by the presence on electrocardiogram at baseline 6MWD or medical history of AF during hospitalization. In statistical analysis, we compared baseline clinical characteristics, QS and 6MWD between the rhythm status (SR group or AF group). We also examined the changes in QS and 6MWD from baseline to the 5-month observation period (ΔQS and Δ6MWD) and compared them between the 2 groups using analysis of covariance with adjustment for baseline clinical confounding factors. Results At baseline, 289 patients (68%) were in SR, and 111 patients (26%) had AF. The AF was associated significantly with older age (P&lt;0.001) and lower levels of estimated glomerular filtration rate (P=0.013), QS (P&lt;0.001) and 6MWD (P&lt;0.001) at baseline. The QS increased significantly from 25.2±11.0 kg at baseline to 30.8±13.0 kg after 5-month cardiac rehabilitation in the SR group, and from 21.1±8.3 kg to 26.0±9.4 kg in the AF group (P&lt;0.001, respectively). The 6MWD also increased significantly from 394.8±129.2 to 463.5±133.5 meters in the SR, and from 343.7±107.9 to 403.0±114.5 meters in the AF (P&lt;0.001, respectively). There were no significant differences in ΔQS and Δ6MWD between the SR and AF groups even after adjustment for clinical confounding factors including baseline QS or 6MWD (Figure). Conclusions The AF status in HFpEF patients was associated with older age, lower peripheral muscle function and also lower exercise tolerance at baseline, but not associated with the responses to exercise training. Acknowledgement/Funding JSPS KAKENHI JP16K16442

1206Doxapram is a promising new antiarrhythmic drug for an atrial-specific therapy of atrial fibrillation

Abstract Background TASK-1 (K2P3.1) is an atrial-specific two-pore domain potassium channel that is significantly upregulated in atrial fibrillation (AF) patients resulting in shortened atrial action potential duration (APD). Inhibition of TASK-1 in human atrial cardiomyocytes reverses AF-related APD shortening to values observed in patients with sinus rhythm (SR). By in silico-modelling and experimental characterization of drug binding sites, doxapram was identified as specific inhibitor of TASK-1. Purpose In this study, we investigated the antiarrhythmic efficacy of doxapram in a porcine model of AF to convert and suppress AF. Methods We established a new porcine model of persistent AF without induced tachymyopathy. AF was induced in domestic pigs by intermittent atrial burst stimulation using implanted pacemakers. During AF episodes, burst stimulation was inhibited by an integrated pacemaker biofeedback algorithm. AV-node ablation was performed to prevent AF-associated heart failure. All pigs underwent catheter-based electrophysiological investigations prior to and after 14 days doxapram treatment. Pigs in the treatment group received intravenous applications of doxapram twice per day. Rhythm status was continuously recorded by intracardiac long-term ECG monitors. The application of doxapram for cardioversion and long term suppression of AF in pigs with persistent AF was evaluated. Subsequent to the doxapram treatment, porcine cardiomyocytes were isolated from right and left atria and electrophysiologically investigated by patch-clamp and multi-electrode experiments. Atrial electrical remodeling was characterized by analyses of ion channel expression at mRNA and protein levels. Results TASK-1 mRNA, protein and transmembrane current were significantly increased in AF pigs compared to SR controls, resulting in shortened atrial APDs. In doxapram-treated AF pigs the AF burden was significantly reduced. After 14 days treatment with doxapram, TASK-1 currents and atrial APDs recorded in porcine cardiomyocytes were reduced and similar to values of SR animals. Doxapram could be successfully applied for cardioversion in pigs with persistent AF. On average, cardioversion was observed 3 minutes after doxapram application. Conclusion Doxapram significantly suppressed AF episodes and normalized cellular electrophysiological characteristics in a porcine model of AF through inhibition of the TASK-1 ion channel. Furthermore, doxapram rapidly converted AF into SR in pigs. Therefore, doxapram might serve as a new antiarrhythmic drug to treat AF in patients.

P1701Sex-related difference in receiving bystander cardiopulmonary resuscitation and clinical outcome among out-of-hospital cardiac arrest patients

Abstract Background Early studies from US and Europe have reported that female out-of-hospital cardiac arrest (OHCA) patients were less likely to receive bystander cardiopulmonary resuscitation (CPR). However, little is known about sex-related difference in receiving CPR and clinical outcome among adult OHCA patients in Japan. Methods This study was a nation-wide, population-based observational study of OHCA in Japan from 2011 to 2015. We included all adult cardiogenic OHCA patients. We excluded patients witnessed by emergency medical services (EMS) from the present analysis. To account for the age-related difference, we stratified by age category: 18–39, 40–64, 65–79, and ≥80. To examine the association between patient sex and neurological outcome at 30-day, we fitted multivariable logistic regression model with adjustment for age, bystander CPR status, first document rhythm, dispatcher instruction and EMS response time. Results There were 339,317 adult cardiogenic, not EMS-witnessed OHCA patients (median age, 80; female, 43.5%) in Japan from 2011 to 2015. Overall, 171,122 (50.4%) received CPR by citizen, 34,283 (10.1%) had initial shockable rhythm, and 11,421 (3.4%) had favorable neurological status at 30-day. Female patients were more likely to receive bystander CPR (vs. male; 53.8% vs. 47.8%), and were less likely to have initial shockable rhythm (5.2% vs. 13.9%) and favorable neurological status at 30-day (1.8% vs. 4.6%) (all; p&lt;0.001). With stratification by age category, elderly female patients (aged ≥65) were more likely to received bystander CPR (P&lt;0.001), whereas male patients were more likely to received bystander CPR among patients aged &lt;40. Multivariable logistic regression analysis showed that female patients had a lower rate of favorable neurological status at 30-day, compared to male patients in all age categories (all; P&lt;0.05). Sex difference in bystander CPR Overall Male (n=191,672) Female (n=147,645) p-value All (n=339,317) 50.4% 47.8% 53.8% &lt;0.001 Aged 18–39 (n=6,216) 56.0% 56.9% 53.5% 0.02 Aged 40–64 (n=50,320) 48.5% 48.5% 48.3% 0.69 Aged 65–80 (n=105,141) 46.5% 45.5% 48.3% &lt;0.001 Aged ≥80 (n=177,640) 53.2% 49.0% 56.7% &lt;0.001 OR for neurological outcome at 30-day Conclusion Unlike the situation in Europe and US, female OHCA patients, especially elderly female, were more likely to receive bystander CPR in Japan. However, female patients had worse clinical outcome after OHCA. Further investigations including in-hospital treatment are needed to clarify the sex-difference in clinical outcome after OHCA. Acknowledgement/Funding None

P2530Frailty assessment in atrial fibrillation patients with acute coronary syndromes: a subanalysis from LONGEVO-SCA registry

Abstract Background Different studies have observed a significant correlation between frailty, morbidity and mortality in elderly patients with cardiovascular diseases.Several scores have been developed to assess frailty in elderly patients. The FRAIL scale is a bed-side and easy tool that evaluates 5 items: fatigue, resistance, ambulation, concomitant diseases and weight loss. However, the evaluation of frailty status in AF patients with ACS is scarce. Purpose The aim of this study was to analyze the management of elderly patients with AF and ACS and the predictive value of frailty for adverse events. Methods The prospective multicentre LONGEVO-SCA enrolled unselected elderly patients hospitalized after non-STACS. In this substudy, we divided patients according to rhythm status (AF or sinus rhythm [SR]) and to frail status. We validated the predictive performance of FRAIL scores for adverse events at 6 months follow-up. Results We analyzed 531 patients (mean age 84.4±3.6 years; 322 (60.6%) male). 128 (24.1%) had AF diagnosis and 145 (27.3%) patients were frail. Frail AF patients had higher risk of global mortality [HR 2.61, (95% CI 1.28–5.31; p=0.008)], readmissions [HR 2.28, (95% CI 1.37–3.80); p=0.002)] and the composite endpoint [HR 2.28, (95% CI 1.44–3.60); p&lt;0.001)] compared with non-frail SR patients. After multivariate adjustment, Frail score [HR 1.41; 95% CI (1.02–1.97); p=0.040] was independently associated with mortality. Kaplan Meier analysis showed that frail AF patients had significantly worse prognosis during the follow-up with high risk of global mortality (log rank p=0.024) and readmission (log rank p&lt;0.001) followed closely by those frail SR patients. Event Free Survival according Frailty Conclusions In the LONGEVO-SCA registry, frail AF patients have 2-fold risk of adverse events compared to non-frail SR patients. Frailty status was an independent condition associated with high risk of adverse events at 6 months of follow-up.

P4784Efficacy and safety of dronedarone by duration of atrial fibrillation history: a post-hoc analysis of the ATHENA trial

Abstract Background Atrial fibrillation (AF) is known to progress over time and the effectiveness of antiarrhythmic therapy may vary based on the duration of a patient's AF history. Outcomes with dronedarone (DRO) based on duration of AF/atrial flutter (AFL) history have not been previously characterized. Purpose To evaluate the efficacy and safety of DRO by time since first known AF/AFL episode in patients studied in the ATHENA trial. Methods 2859 (61.8%) patients from ATHENA with documented first known AF/AFL episode (of 4628 total patients randomized) were included in the analysis. Among these patients, first AF/AFL episode was reported at &lt;3 months (shorter history), 3 to &lt;24 months (intermediate), and ≥24 months (longer) in 1296 (45.3%), 845 (29.6%) and 718 (25.1%) patients, respectively. AF/AFL recurrence was evaluated in patients in sinus rhythm at baseline by ECG during study visits or symptom recurrence. Results Demographics (age, sex) were similar across all groups. Patients with longer AF/AFL history tended to have higher prevalence of coronary heart disease and structural heart disease; and were more likely to have AF/AFL (by 12-lead ECG) at baseline (30%) compared to 26% and 16% for intermediate and shorter history groups. Patients with a longer AF history likely had a prior ablation for AF/AFL (7%) vs patients with an intermediate (2%) or shorter AF/AFL history (1%), and more likely required cardioversion during the study (24%) vs intermediate (17%) and shorter history groups (11%). Outcomes and efficacy are reported in Table 1. Rates of treatment-emergent adverse events (TEAEs), serious TEAEs, permanent drug discontinuations, and deaths were similar across all AF/AFL groups. Table 1. Outcomes and efficacy summary Relative Risk, dronedarone (DRO) vs placebo (PBO)1 (95% CI)1,2 AF/AFL &lt;3 months AF/AFL 3 to &lt;24 months AF/AFL ≥24 months PBO (n=626) DRO (n=670) PBO (n=429) DRO (n=416) PBO (n=363) DRO (n=355) First CV hospitalization3 or death (any cause) 0.79 (0.65, 0.96) 0.72 (0.56, 0.92) 0.84 (0.66, 1.07) First CV hospitalization 0.78 (0.64, 0.96) 0.70 (0.55, 0.91) 0.82 (0.63, 1.05) Death (any cause) 0.82 (0.54, 1.24) 0.85 (0.43, 1.68) 1.13 (0.61, 2.10) First AF/AFL recurrence4 0.80 (0.65, 0.97) 0.67 (0.53, 0.84) 0.81 (0.65, 1.02) 1Cox regression model. 2On study period, all randomized patients. 3Main reason was AF/other supraventricular rhythm disorders. 4On selected patients in sinus rhythm at baseline (AF/AFL &lt;3 months: PBO n=514, DRO n=529; 3 to &lt;24 months: PBO n=288, DRO n=312; ≥24 months: PBO n=252, DRO n=250). CV = Cardiovascular. Conclusions Nearly half the patients in ATHENA had a shorter history (&lt;3 months) of AF/AFL prior to randomization. Patients with a longer history of AF/AFL had a greater burden of AF/AFL based on baseline rhythm status, ablation history, and cardioversions required post randomization. Despite these differences, clinical outcomes, efficacy, and safety of DRO appeared to be generally consistent irrespective of duration of AF/AFL history. Acknowledgement/Funding Sanofi, New York, New York, United States of America

A Standardized Extract of Asparagus officinalis Stem (ETAS®) Ameliorates Cognitive Impairment, Inhibits Amyloid β Deposition via BACE-1 and Normalizes Circadian Rhythm Signaling via MT1 and MT2.

The prevalence of cognitive impairments and circadian disturbances increases in the elderly and Alzheimer’s disease (AD) patients. This study investigated the effects of a standardized extract of Asparagus officinalis stem, ETAS® on cognitive impairments and circadian rhythm status in senescence-accelerated mice prone 8 (SAMP8). ETAS® consists of two major bioactive constituents: 5-hydroxymethyl-2-furfural (HMF), an abundant constituent, and (S)-asfural, a novel constituent, which is a derivative of HMF. Three-month-old SAMP8 male mice were divided into a control, 200 and 1000 mg/kg BW ETAS® groups, while senescence-accelerated resistant mice (SAMR1) were used as the normal control. After 12-week feeding, ETAS® significantly enhanced cognitive performance by an active avoidance test, inhibited the expressions of amyloid-beta precursor protein (APP) and BACE-1 and lowered the accumulation of amyloid β (Aβ) in the brain. ETAS® also significantly increased neuron number in the suprachiasmatic nucleus (SCN) and normalized the expressions of the melatonin receptor 1 (MT1) and melatonin receptor 2 (MT2). In conclusion, ETAS® enhances the cognitive ability, inhibits Aβ deposition and normalizes circadian rhythm signaling, suggesting it is beneficial for preventing cognitive impairments and circadian rhythm disturbances in aging.

Antiarrhythmic drug therapy and all-cause mortality after catheter ablation of atrial fibrillation: A propensity-matched analysis

It is not clear if antiarrhythmic drug therapy (AAD) after catheter ablation (CA) of atrial fibrillation (AF) increases mortality. To determine whether there is an association between AAD therapy and mortality after CA of AF. There were 3624 consecutive patients with AF (mean age: 59 ± 11 years, women: 27%, paroxysmal AF: 58%). An AAD was used in 2253 patients (62%, AAD group) for a mean duration of 1.3 ± 0.8 years, during a mean follow-up of 6.7 ± 2.2 years after CA of AF. Using propensity score matching, with every 2 patients using an AAD matched to 1 patient who did not use AAD (NO-AAD group), Cox regression models were utilized to assess the association between AAD use (as a time-variable covariate) and all-cause mortality. There were a total of 50 deaths (2.2%) in the AAD and 62 deaths (4.5%) in the NO-AAD groups, respectively (P = .02). At the time of death, 46 of 50 patients (92%) who died in the AAD cohort were still using an AAD (P = .21, compared to baseline use). On multivariate analysis, although the risk of death was not statistically significant between the AAD and NO-AAD cohorts, there was a trend towards mortality benefit with AAD therapy (hazard ratio [HR]: 0.66, 95% confidence interval [CI]: 0.43-1.00, P = .05), regardless of the rhythm or anticoagulation status. AAD use after CA of AF is not associated with an increased risk of mortality, suggesting that when carefully chosen and monitored, AADs appear to be safe after CA of AF.

Early arrhythmia burden in pediatric cardiac surgery fast-track candidates: Analysis of incidence and risk factors

An increasing number of pediatric heart centers are utilizing early extubation protocols to “fast-track” patients after congenital heart surgery. Early postoperative arrhythmias are an important recognized complication of pediatric heart surgery, but the arrhythmia burden among candidates for extubation immediately after bypass surgery is unknown. This study evaluated the incidence and risk factors associated with postoperative arrhythmias in surgical fast-track candidates.Postoperative rhythm status and potential perioperative risk factors were retrospectively analyzed in all patients undergoing surgery for congenital heart disease from 2012 to 2014 who were considered early extubation candidates. Overall, 199 operations in 196 individual patients (30 days–19 years) were included. The overall incidence of arrhythmias was 9% (18/199). The most common arrhythmia was junctional ectopic tachycardia (5%; 10/199), followed by atrial tachycardia (1.5%; 3/199) and complete heart block (1.5%; 3/199). Two patients with junctional ectopic tachycardia had permanent complete heart block. Compared to patients with no arrhythmias, patients with arrhythmias were more likely to be younger (0.5 vs. 2.4 years, U = 783, p < 0.001) and to weigh less (6.0 vs.12 kg, U = 853, p < 0.005). Surgical repairs with the highest incidence of arrhythmia were tetralogy of Fallot-type (6/18, 33%; p = 0.017), followed by repair of atrioventricular canal (5/18, 28%, p = 0.022) and ventricular septal defect repair (4/18, 22%, p = 0.758). In an unadjusted analysis, younger patient age, STAT category 4 procedures, and increasing cross-clamp time were significantly associated with the occurrence of arrhythmias. Amiodarone and procainamide were the most common drugs used for junctional ectopic tachycardia and atrial tachycardia. There were no deaths related to postoperative arrhythmias.Early postoperative arrhythmias are common among fast-track candidates. Patient age and operation complexity may predict risk of early arrhythmia. These data provide important information to help guide programmatic and clinical decision-making when contemplating fast tracking children after congenital heart surgery.