Ambulatory Rhythm Research Articles

Association of functioning and quality of life with objective and subjective measures of sleep and biological rhythms in major depressive and bipolar disorder.

Disruptions in biological rhythms and sleep are a core aspect of mood disorders, with sleep and rhythm changes frequently occurring prior to and during mood episodes. Wrist-worn actigraphs are increasingly utilized to measure ambulatory activity rhythm and sleep patterns. A comprehensive study using subjective and objective measures of sleep and biological rhythms was conducted in 111 participants (40 healthy volunteers [HC], 38 with major depressive disorder [MDD] and 33 with bipolar disorder [BD]). Participants completed 15-day actigraphy and first-morning urine samples to measure 6-sulfatoxymelatonin levels. Sleep and biological rhythm questionnaires were administered: Biological Rhythms Interview of Assessment in Neuropsychiatry (BRIAN), Munich Chronotype Questionnaire (MCTQ), Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS). Actigraph data were analyzed for sleep and daily activity rhythms, light exposure and likelihood of transitioning between rest and activity states. Mood groups had worse subjective sleep quality (PSQI) and biological rhythm disruption (BRIAN) and higher objective mean nighttime activity than controls. Participants with BD had longer total sleep time, higher circadian quotient and lower 6-sulfatoxymelatonin levels than HC group. The MDD group had longer sleep onset latency and higher daytime probability of transitioning from rest to activity than HCs. Mood groups displayed later mean timing of light exposure. Multiple linear regression analysis with BRIAN scores, circadian quotient, mean nighttime activity during rest and daytime probability of transitioning from activity to rest explained 43% of variance in quality-of-life scores. BRIAN scores, total sleep time and probability of transitioning from activity to rest explained 52% of variance in functioning (all p < 0.05). Disruption in biological rhythms is associated with poorer functioning and quality of life in bipolar and MDD. Investigating biological rhythms and sleep using actigraphy variables, urinary 6-sulfatoxymelatonin and subjective measures provide evidence of widespread sleep and circadian system disruptions in mood disorders.

A Novel Wearable Device for Continuous Ambulatory ECG Recording: Proof of Concept and Assessment of Signal Quality

Diagnosis of arrhythmic disorders is challenging because of their short-lasting, intermittent character. Conventional technologies of noninvasive ambulatory rhythm monitoring are limited by modest sensitivity. We present a novel form of wearable electrocardiogram (ECG) sensors providing an alternative tool for long-term rhythm monitoring with the potential of increased sensitivity to detect intermittent or subclinical arrhythmia. The objective was to assess the signal quality and R-R coverage of a wearable ECG sensor system compared to a standard 3-lead Holter. In this phase-1 trial, healthy individuals underwent 24-h simultaneous rhythm monitoring using the OMsignal system together with a 3-lead Holter recording. The OMsignal system consists of a garment (bra or shirt) with integrated sensors recording a single-lead ECG and an acquisition module for data storage and processing. Head-to-head signal quality was assessed regarding adequate P-QRS-T distinction and was performed by three electrophysiologists blinded to the recording technology. The accuracy of signal coverage was assessed using Bland-Altman analysis. Fifteen individuals underwent simultaneous 24-h recording. Signal quality and accuracy of the OMgaments was equivalent to Holter-monitoring (84% vs. 93% electrophysiologists rating, p = 0.06). Signal coverage of R-R intervals showed a very close overlay between the OMsignal system and Holter signals, mean difference in heart rate of 2 ± 5 bpm. The noise level of OMgarments was comparable to Holter recording. OMgarments provide high signal quality for adequate rhythm analysis, representing a promising novel technology for long-term non-invasive ECG monitoring.

Extended cardiac ambulatory rhythm monitoring in adults with congenital heart disease: Arrhythmia detection and impact of extended monitoring.

Arrhythmias are a leading cause of death in adults with congenital heart disease (ACHD). While 24-48-hour monitors are often used to assess arrhythmia burden, extended continuous ambulatory rhythm monitors (ECAM) can record 2 weeks of data. The utility of this device and the arrhythmia burden identified beyond 48-hour monitoring have not been evaluated in the ACHD population. Additionally, the impact of ECAM has not been studied to determine management recommendations. To address the preliminary question, we hypothesized that clinically significant arrhythmias would be detected on ECAM beyond 48hours and this would lead to clinical management changes. A single center retrospective cohort study of ACHD patients undergoing ECAM from June 2013 to May 2016 was performed. The number and type of arrhythmias detected within and beyond the first 48hours of monitoring were compared using Kaplan-Meier curves and Cox proportional hazard models. Three hundred fourteen patients had monitors performed [median age 31 (IQR 25-41) years, 61% female). Significant arrhythmias were identified in 156 patients (50%), of which 46% were noted within 48 hours. A management change based on an arrhythmia was made in 49 patients (16%). ECAM detects more clinically significant arrhythmias than standard 48-hour monitoring in ACHD patients. Management changes, including medication changes, further testing or imaging, and procedures, were made based on results of ECAM. Recommendations and guidelines have been made based on arrhythmias on 48-hour monitoring; the predictive ability and clinical consequence of arrhythmias found on ECAM are not yet known.

New atrial fibrillation diagnosed by 30-day rhythm monitoring

Recent studies of patients with pacemakers and implantable cardioverter/defibrillators have shown that subclinical atrial fibrillation (AF) is common and is associated with thromboembolic risk. We sought to evaluate the frequency, characteristics, and impact of new AF diagnosed by ambulatory 30-day rhythm monitoring. The 30-day rhythm monitoring data from January 2010 to August 2015 at our institution were reviewed. Medical record review was performed on patients that had a new or preexisting diagnosis of AF. Of 2,326 patients without a previous diagnosis of AF, 78 had a new diagnosis of AF (3.4%) during 30-day monitoring. Patients with a new diagnosis of AF (mean age of 68.5 years, 56% female) had a mean CHA2DS2-VASc score of 3.2 (±1.8). The median time to diagnosis was 6 days, and 86% were diagnosed within 14 days. In 31 patients (40%), AF was exclusively detected automatically by the monitor. Of 46 patients that had manually activated the monitor, 34 also had automatically detected AF. Each patient had a median of 7 episodes, with the median duration of the longest episode being approximately 2 hours. Following the diagnosis of AF, 37 (47%) were started on anticoagulation and 9 (12%) were prescribed aspirin. A total of 3.4% of patients who underwent 30-day rhythm monitoring for any indication were found to have a new diagnosis of AF (402 per 1000 patient-years). Most of these episodes were detected automatically, corresponding to device-detected subclinical AF. The most common intervention following diagnosis of AF was initiation of oral anticoagulation.

A Pilot Randomized Trial of Oral Magnesium Supplementation on Supraventricular Arrhythmias.

Low magnesium may increase the risk of atrial fibrillation. We conducted a double-blind pilot randomized trial to assess adherence to oral magnesium supplementation (400 mg of magnesium oxide daily) and a matching placebo, estimate the effect on circulating magnesium concentrations, and evaluate the feasibility of using an ambulatory heart rhythm monitoring device (ZioPatch) for assessing premature atrial contractions. A total of 59 participants were randomized; 73% were women, and the mean age was 62 years. A total of 98% of the participants completed the follow-up. In the magnesium supplement group, 75% of pills were taken, and in the placebo group, 83% were taken. The change in magnesium concentrations was significantly greater for those given the magnesium supplements than for those given the placebo (0.07; 95% confidence interval: 0.03, 0.12 mEq/L; p = 0.002). The ZioPatch wear time was approximately 13 of the requested 14 days at baseline and follow-up. There was no difference by intervention assignment in the change in log premature atrial contractions burden, glucose, or blood pressure. Gastrointestinal changes were more common among the participants assigned magnesium (50%) than among those assigned the placebo (7%), but only one person discontinued participation. In sum, compliance with the oral magnesium supplementation was very good, and acceptance of the ZioPatch monitoring was excellent. These findings support the feasibility of a larger trial for atrial fibrillation (AF) prevention with oral magnesium supplementation.

Clinical impact of a novel ambulatory rhythm monitor in children.

Traditional ambulatory rhythm monitoring in children can have limitations, including cumbersome leads and limited monitoring duration. The ZioTM patch ambulatory monitor is a small, adhesive, single-channel rhythm monitor that can be worn up to 2 weeks. In this study, we present a retrospective cross-sectional analysis of the ZioTM monitor's impact in clinical practice. Patients aged 0-18 years were included in the study. A total of 373 studies were reviewed in 332 patients. In all, 28.4% had structural heart disease, and 16.9% had a prior surgical, catheterisation, or electrophysiology procedure. The most common indication for monitoring was tachypalpitations (41%); 93.5% of these patients had their symptoms captured during the study window. The median duration of monitoring was 5 days. Overall, 5.1% of ZioTM monitoring identified arrhythmias requiring new intervention or increased medical management; 4.0% identified arrhythmias requiring increased clinical surveillance. The remainder had either normal-variant rhythm or minor rhythm findings requiring no change in management. For patients with tachypalpitations and no structural heart disease, 13.2% had pathological arrhythmias, but 72.9% had normal-variant rhythm during symptoms, allowing discharge from cardiology care. Notably, for patients with findings requiring intervention or increased surveillance, 56% had findings first identified beyond 24 hours, and only 62% were patient-triggered findings. Seven studies (1.9%) were associated with complications or patient intolerance. The ZioTM is a well-tolerated device that may improve what traditional Holter and event monitoring would detect in paediatric cardiology patients. This study shows a positive clinical impact on the management of patients within a paediatric cardiology practice.

Validation of a genetic risk score for atrial fibrillation: A prospective multicenter cohort study

BackgroundAtrial fibrillation (AF) is the most commonly encountered arrhythmia and is associated with an elevated risk of stroke. Improving the identification of patients with the highest risk for AF to enable appropriate surveillance and treatment, if necessary, is critical to reducing AF-associated morbidity and mortality. Multiple common single nucleotide polymorphisms (SNPs) are unequivocally associated with the lifetime risk of AF. In the current study we aimed to prospectively validate an AF genetic risk score (GRS) in previously undiagnosed patients at risk for AF.Methods and findingsIndividuals 40 years of age or older with 1 clinical risk factor for AF, presenting with symptoms of AF, or with a first diagnosis of AF, were enrolled for genetic testing and ambulatory cardiac rhythm monitoring with an adhesive patch monitor or a long-term Holter monitor (mean wear time 10 days 21 hours and 13 days 18 hours, respectively). An AF event was the first diagnosis of AF by ECG, patch monitor, or long-term Holter monitor. The AF GRS was determined for each participant based on the weighted contribution of 12 genetic risk loci. Of 904 participants, 85 manifested AF. Their mean age was 66.2 (SD 11.8) years; 38% of participants were male. Participants in the highest quintile of AF GRS were more likely (odds ratio 3.11; 95% CI 1.27–7.58; p = 0.01) to have had an AF event than participants in the lowest quintile after adjusting for age, sex, smoking status, BMI, hypertension, diabetes mellitus, heart failure, and prior myocardial infarction. Study limitations included an ethnically homogenous population, a restricted rhythm monitoring period, and the evolving discovery of SNPs associated with AF.ConclusionsProspective assessment of a GRS for AF identified participants with elevated risk of AF beyond established clinical criteria. Accordingly, a GRS for AF could be incorporated into overall risk assessment to better identify patients at the highest risk of developing AF, although further testing in larger populations is needed to confirm these findings.Trial registrationClinicalTrials.gov NCT01970969

Causes of ‘Unclassified’ Automated Diagnoses on a Smartphone Based Single-Lead Electrocardiogram Platform

Background: The AliveCor heart rate monitor (AHM) is a Food and Drug Administration-approved hand-held ambulatory cardiac rhythm monitor that records a lead-I electrocardiogram (ECG) strip when paired with a smartphone. On population screening studies, up to one in four tracings are ‘unclassified’ by device algorithms. However, there is a lack of data on the causes of an ‘unclassified’ tracing and the proportion of undetected arrhythmias in this cohort.

The Right Heart: Acute and Chronic Issues.

Cardiovascular remodeling in response to sustained moderate and high-intensity exercise is a well-established phenomenon. Following more than a century of work focused on the left ventricle (LV), remodeling of the right side of the heart has recently become a topic of considerable scientific and clinical interest. Morphologic and functional changes have now been well documented in the right ventricle (RV) after isolated bouts of endurance exercise and in association with long-term sustained training. Although exercise-induced cardiac remodeling is classically viewed as an adaptive, clinically benign process, it has recently been hypothesized that repetitive bouts of intense exercise may trigger pathologic changes in the RV characterized by patchy fibrosis and a predisposition to arrhythmia. At present, this concept remains speculative due to the absence of definitive clinical data. While we await scientific clarification of this intriguing hypothesis, several practical clinical considerations are noteworthy. RV dilation is common among trained endurance athletes. As such, asymptomatic athletes with RV dilation do not require additional diagnostic evaluation unless dilation is accompanied by substantial decrements in systolic function or other structural abnormalities suggestive of genetic heart disease. In contrast, RV dilation among athletes with either symptoms or a family history of genetic heart disease requires extensive multi-modality assessment including maximal effort-limited exercise testing, ambulatory rhythm monitoring, advanced non-invasive imaging, and invasive electrophysiology study. This review will discuss the contemporary understanding of how the RV responds to exercise with an emphasis on the relevance of this phenomenon in clinical cardiovascular practice.

Point-of-Care Utilisation of Single Lead Smartphone Electrocardiogram in Screening for Arrhythmias: PULSE Trial

Background: AliveCor Heart Rate Monitor (AHM) is an FDA approved hand-held ambulatory cardiac rhythm monitor that records a Lead-I ECG strip when paired with a smartphone. Having demonstrated efficacy in population screening for AF, these devices are marketed to patients as offering medical grade diagnostic capabilities. A paucity of data exists regarding accuracy of clinician interpretation of cardiac rhythm from smartphone-based electrocardiograms. Methods: Patients that underwent cardioversion between July 2016 and January 2017 for AF/atrial flutter were prospectively recruited. Three AHM traces and a 12-lead ECG was recorded- pre and post cardioversion. Two electrophysiologists and general practitioners, blinded to the clinical data, 12-lead-ECG and AHM interpretation assessed each AHM trace independently on an iPhone 6-Plus smartphone. Results: 408 ECG tracings (306 AHM, 102 12-lead ECGs) were recorded from fifty-one patients (mean age 63 ± 14 years). Accuracy of both clinician and automated device diagnosis were compared (Table). Only 2% of AHM tracings were uninterpretable by clinicians as opposed to 15% by the AHM algorithm. Conclusions: Clinician interpretation of a smartphone-based ECG has excellent accuracy for diagnosis of AF but poor sensitivity for diagnosis of atrial flutter. This supports its versatility as a point-of-care device by both cardiologists and GPs in an inpatient or outpatient setting.Tabled 1RhythmElectrophysiologistsGeneral PractitionersAliveCor Auto-Dx(ECG)SensitivitySpecificitySensitivitySpecificitySensitivitySpecificitySinus Rhythm96%88%94%82%78%98%AF87%97%82%91%89%78%A. Flutter28%96%14%82%43%78% Open table in a new tab

Potential Cost-Effectiveness of Ambulatory Cardiac Rhythm Monitoring After Cryptogenic Stroke.

Prolonged ambulatory ECG monitoring after cryptogenic stroke improves detection of covert atrial fibrillation, but its long-term cost-effectiveness is uncertain. We estimated the cost-effectiveness of noninvasive ECG monitoring in patients aged ≥55 years after a recent cryptogenic stroke and negative 24-hour ECG. A Markov model used observed rates of atrial fibrillation detection and anticoagulation from a randomized controlled trial (EMBRACE) and the published literature to predict lifetime costs and effectiveness (ischemic strokes, hemorrhages, life-years, and quality-adjusted life-years [QALYs]) for 30-day ECG (primary analysis) and 7-day or 14-day ECG (secondary analysis), when compared with a repeat 24-hour ECG. Prolonged ECG monitoring (7, 14, or 30 days) was predicted to prevent more ischemic strokes, decrease mortality, and improve QALYs. If anticoagulation reduced stroke risk by 50%, 30-day ECG (at a cost of USD $447) would be highly cost-effective ($2000 per QALY gained) for patients with a 4.5% annual ischemic stroke recurrence risk. Cost-effectiveness was sensitive to stroke recurrence risk and anticoagulant effectiveness, which remain uncertain, especially at higher costs of monitoring. Shorter duration (7 or 14 days) monitoring was cost saving and more effective than an additional 24-hour ECG; its cost-effectiveness was less sensitive to changes in ischemic stroke risk and treatment effect. After a cryptogenic stroke, 30-day ECG monitoring is likely cost-effective for preventing recurrent strokes; 14-day monitoring is an attractive value alternative, especially for lower risk patients. These results strengthen emerging recommendations for prolonged ECG monitoring in secondary stroke prevention. Cost-effectiveness in practice will depend on careful patient selection.

Diagnostic Yield of a 14 Day Ambulatory ECG Recorder in Patients With Suspected Syncope

Purpose: To evaluate the diagnostic yield of a leadless continuous ECG recording patch (Zio) worn for up to 14 days in patients with prior syncopal history. Introduction: Ambulatory heart rhythm recording is a mainstay in the work-up of unexplained syncope. The diagnostic yield of older devices such as Holter and external event recorders is low, raising the question of the optimal ECG monitoring device and duration for the evaluation of syncope. We sought to assess the diagnostic yield of a leadless continuous ECG recording patch (Zio) worn for up to 14 days in patients with prior syncopal history. Methods: ECG tracings and patient reported symptoms from devices prescribed by an academic cardiology practice for a history of syncope were reviewed. Symptoms were documented by patients via a trigger button as well as by diary entry. Arrhythmias were defined as: pause greater than 3 seconds, bradycardia less than 40bpm, supraventricular tachycardia lasting longer than 30 seconds and sustained ventricular tachycardia. Results: From 12/ 2010-11/2014, sixty-eight patients were identified from a database of 1030 unique patient studies, 71% female, with a mean age 52 (range 16-102). The average monitoring period was 7d 10hrs (range 2d 9hrs to 14d). A total of 12 arrhythmias were captured in 5 patients (4 patients with 1 arrhythmia, 1 patient with 8). Bradycardia !40bpm occurred in 4 patients (6%), pause O3 seconds in 1 patient (1.5%) and supraventricular tachycardia O30 seconds in 1 patient (1.5%). Two hundred and twenty two triggers (3.3 per pt, range 0-33) and 120 diary entries (1.8 per pt, range 0-8) were recorded. There were 45 diary entries for pre-syncope and none for syncope. None of the triggers or documented symptoms correlated with the captured arrhythmias. Conclusion: Among patients strongly suspected of an arrhythmic basis for syncope, the diagnostic yield of patch recording up to 14 days in capturing significant arrhythmias is low. However, syncopal events were not documented during the wear period. These results would support the use of ECG monitoring systems with even longer recording windows and quick patient accessibility such as implantable devices or smart-phone connected patient acquired ECG systems.

İnvaziv Olmayan Ventilasyon Kullanan Kronik Solunum Yetersizlikli Kifoskolyoz Hastalarının Kardiyak Fonksiyonlarının ve Total Mortalitenin Değerlendirilmesi

Introduction: We aimed to evaluate cardiac functions and mortality rate in kyphoscoliosis patients with chronic respiratory failure under long term non-invasive ventilation (NIV). Patients and Methods: Kyphoscoliosis patients, who used NIV, were included in the study. Patients' characteristics and cardiovascular risk factors were recorded. Ambulatory rhythm monitoring and echocardiography were performed for all patients. Results were compared with 26 age-gender matched volunteers without dyspnea. Patients had been followed for five years. Results: Twenty-three kyphoscoliosis patients (54 ± 13 years, 15 male) were included in the study. Hypertension and paroxysmal atrial fibrillation were more frequent in patients. Left ventricular systolic functions were normal but diastolic functions were worsened. Right ventricular sizes were normal but systolic and diastolic functions were worsened and the mean pulmonary artery pressure was higher in kyphoscoliosis patients. Four patients were died in follow up. Two of patients died due to severe hypoxia and two of them died due to sepsis. Clinical and laboratory properties including cardiovascular risk factors, echocardiographic examination were not different between the survived patients and dying ones. Conclusion: Hypertension and arrhythmia are more frequent. The left ventricle is slightly affected but the right ventricle is severely affected and pulmonary pressure is increased in kyphoscoliosis. Cardiovascular functions do not predict mortality in kyphoscoliosis patients under long term NIV treatment.

Surface 12 lead electrocardiogram recordings using smart phone technology

ImportanceAliveCor ECG is an FDA approved ambulatory cardiac rhythm monitor that records a single channel (lead I) ECG rhythm strip using an iPhone. In the past few years, the use of smartphones and tablets with health related applications has significantly proliferated. ObjectiveIn this initial feasibility trial, we attempted to reproduce the 12 lead ECG using the bipolar arrangement of the AliveCor monitor coupled to smart phone technology. MethodsWe used the AliveCor heart monitor coupled with an iPhone cellular phone and the AliveECG application (APP) in 5 individuals. ResultsIn our 5 individuals, recordings from both a standard 12 lead ECG and the AliveCor generated 12 lead ECG had the same interpretation. ConclusionsThis study demonstrates the feasibility of creating a 12 lead ECG with a smart phone. The validity of the recordings would seem to suggest that this technology could become an important useful tool for clinical use. This new hand held smart phone 12 lead ECG recorder needs further development and validation.

Abstract W MP63: Diagnostic Yield of an Extended Ambulatory Cardiac Rhythm Monitor in Patients With TIA or Stroke

Background: In the evaluation of patients with TIA or stroke, the detection of AF changes the recommended anti-thrombotic regimen from treatment with an antiplatelet agent to oral anticoagulation. Detection of supraventricular tachycardia (SVT) may also be relevant as it is associated with an increased risk of AF. This study describes the feasibility and diagnostic yield of the Zio® Patch, a leadless, single-use, small, lightweight, and water-resistant cardiac rhythm monitor that provides continuous cardiac monitoring for up to 14 days. Methods: We obtained de-identified monitoring data from the manufacturer and servicer of the ZioPatch (iRhythm Technologies). Patients who were monitored between January 2012 and June 2013 and whose indication for monitoring, as entered by the ordering provider, was TIA or stroke were included. The duration of monitoring, the number and type of arrhythmias, and the time to first arrhythmia were documented. AF was defined as R-R irregularity for more than 30 seconds in duration. Results: 1,171 monitoring reports were analyzed. The average patient age was 67.9 years. Fifty-five percent of patients were male. The mean monitor wear time was 10.9 days and the median wear time was 13.0 days (interquartile range 7.2-14.0). The median analyzable time relative to the total wear time was 98.7% (IQR 96.0-99.5%). AF was present in 4.8% of all reports (4.2% PAF and 0.6% chronic AF). The mean duration before the first episode of PAF was 1.5 days and the median duration was 0.4 days. 14.3% of first PAF episodes occurred after 48 hours. The mean PAF burden was 12.7% of the total monitoring duration. SVT of 8 beats or more was present in 51% of the records. Conclusion: Virtually the entire duration of monitoring with the ZioPatch yields analyzable data that allows for the detection of cardiac arrhythmias. Among TIA and stroke patients, AF was present in approximately 5% of the records and SVT in 50%. The first episode of PAF frequently occurred more than 48 hours after the start of monitoring. This suggests that Holter (24-48 hour) monitoring is insufficient and supports extended cardiac monitoring in TIA and stroke patients. Further studies are needed to determine which stroke patients are at greatest risk for AF and to assess the clinical significance of SVT.

Thoracoscopic Resection of the Left Atrial Appendage After Failed Focal Atrial Tachycardia Ablation

This case series describes 3 patients with the unusual location of focal atrial tachycardia in the left atrial appendage who failed catheter ablation but were successfully treated by left atrial appendage resection by a totally thoracoscopic surgical technique. In all 3 cases, left atrial appendage resection was carried out by video-assisted thoracoscopic surgery using only 3 5- to 10-mm incisions, eliminating the need for median sternotomy or thoracotomy. An endoscopic stapler was used to resect the left atrial appendage at its base, successfully eliminating the source of the patients' focal atrial tachycardia. The mean operative time was 84 minutes. All3 patients tolerated the procedure without any complications and were discharged on postoperative day 3. At an average follow-up of 4.5 years, all patients remained asymptomatic and with normal ambulatory rhythm monitoring off all antiarrhythmic medications. Surgical resection of the left atrial appendage using a totally thoracoscopic approach is a safe and successful treatment option for patients who have failed endocardial catheter ablation. This novel approach utilizes smaller incisions and shorter operative times than the more invasive surgical techniques previously described in the literature.

Abstract 285: Overexpression of SK3 in a Murine Model Results in Sudden Cardiac Death

Background: Recently, the gene responsible for encoding SK3, KCNN3, was implicated in a genome-wide association study as a susceptibility locus for atrial fibrillation. SK3 is one of a family of three small conductance, voltage-independent, calcium-activated potassium channels which is abundantly expressed in cardiac tissues. Therefore, we hypothesized that transcriptional misregulation of the KCNN3 gene could result in arrhythmogenesis. Methods: We characterized a mouse line which had constitutive ubiquitous overexpression of Kcnn3 using ambulatory cardiac rhythm monitoring, optical mapping and in vivo electrophysiology studies. Both homozygote (SK3 T/T ) and heterozygote (SK3 T/+ ) animals were compared to their wild-type (SK3 +/+ ) littermates for assessment of cardiac phenotypes. Results: SK3 T/T mice displayed increased expression of SK3, as assessed by qRT-PCR, in all four chambers of the heart, although highest increase of expression was observed in the ventricles. Examinations of SK3 T/T mice revealed no gross morphological changes in the myocardium, no observable cardiac fibrosis, and normal echocardiograms when compared to SK3 +/+ mice. However, pups from SK3 T/+ crosses did not produce expected Mendelian ratios (SK3 +/+ = 17%), and 7 out of 19 SK3 +/+ mice died suddenly by 3 months of age, whereas all of the SK3 T/+ or SK3 +/+ survived. To address potential mechanisms, we performed ambulatory monitoring on mice beginning at approximately one month of age. Of the 6 SK3 +/+ mice, 4 died suddenly, whereas neither of the wild-type controls expired. The cardiac rhythm recorded at the time of death in three of the four mice was heart block followed by severe bradycardia. Additionally, during the period of ambulatory monitoring, SK3 T/T mice had a lower mean heart rate compared to the SK3 +/+ control mice, and SK3 T/T mice also displayed frequent episodes of atrioventricular dissociation, both at rest and during periods of activity. SK3 T/T mice also displayed more pronounced variability of the heart rate and the PR interval. Optical mapping revealed slower ventricular conduction velocity. Conclusion: These data suggest a mechanism whereby overexpression of SK3 leads to sudden death due to bradyarrhythmias and heart block.

Relation of Atrial Fibrillation Burden and N-Terminal Pro-Brain Natriuretic Peptide

Previous studies have noted a correlation between the presence of atrial fibrillation (AF) and elevated brain natriuretic peptide hormone level, although the exact nature of this association is unclear. Understanding the relation between AF and brain natriuretic peptide may enhance care for this patient population. The aim of this study was to establish the relationship between AF burden and N-terminal pro-brain natriuretic peptide (NT-proBNP) level. One hundred eighty-four patients who presented to the University of North Carolina electrophysiology clinic with AF underwent baseline questionnaires, laboratory testing (including NT-proBNP), echocardiography, and 1-week ambulatory rhythm monitoring. Multivariate linear regression was used to determine the association between AF burden and NT-proBNP level. Increased AF burden was associated with increased NT-proBNP level, and this association remained significant after adjusting for possible confounders. Compared with a 0% AF burden, those with an AF burden of 1% to 25% had a nearly 1.5-fold increase (p = 0.102), those with an AF burden of 26% to 99% had a nearly fourfold increase (p <0.001), and those with an AF burden of 100% had a nearly 4.5-fold increase (p <0.001). In conclusion, AF burden as assessed by continuous 1-week ambulatory rhythm monitoring is directly associated with NT-proBNP level. NT-proBNP may act as a useful surrogate for assessing AF burden.

Use of a Noninvasive Continuous Monitoring Device in the Management of Atrial Fibrillation: A Pilot Study

BackgroundOutpatient ambulatory cardiac rhythm monitoring is a routine part of the management of patients with paroxysmal atrial fibrillation (AF). Current systems are limited by patient convenience and practicality.MethodsWe compared the Zio® Patch, a single-use, noninvasive waterproof long-term continuous monitoring patch, with a 24-hour Holter monitor in 74 consecutive patients with paroxysmal AF referred for Holter monitoring for detection of arrhythmias.ResultsThe Zio® Patch was well tolerated, with a mean monitoring period of 10.8 ± 2.8 days (range 4–14 days). Over a 24-hour period, there was excellent agreement between the Zio® Patch and Holter for identifying AF events and estimating AF burden. Although there was no difference in AF burden estimated by the Zio® Patch and the Holter monitor, AF events were identified in 18 additional individuals, and the documented pattern of AF (persistent or paroxysmal) changed in 21 patients after Zio® Patch monitoring. Other clinically relevant cardiac events recorded on the Zio® Patch after the first 24 hours of monitoring, including symptomatic ventricular pauses, prompted referrals for pacemaker placement or changes in medications. As a result of the findings from the Zio® Patch, 28.4% of patients had a change in their clinical management.ConclusionsThe Zio® Patch was well tolerated, and allowed significantly longer continuous monitoring than a Holter, resulting in an improvement in clinical accuracy, the detection of potentially malignant arrhythmias, and a meaningful change in clinical management. Further studies are necessary to examine the long-term impact of the use of the Zio® Patch in AF management.

Abstract 2500: Paroxysmal Atrial Fibrillation Detected By Prolonged Ambulatory Cardiac Monitoring In Patients With Cryptogenic Stroke: A Case-Control Study

Background: Whether a significant proportion of cryptogenic stroke (CS) is caused by under-detected paroxysmal atrial fibrillation (PAF) is not known. Prolonged ambulatory cardiac monitoring may detect episodes of PAF in patients with stroke of unknown cause (cryptogenic stroke, CS). However, it is unclear whether PAF is more common in patients wtih CS compared with patients with stroke of known cause (SKC). We performed a case control study to compare the rates of detection of PAF in CS vs SKC using prolonged ambulatory cardiac rhythm monitoring. Methods and Results: We prospectively enrolled 132 patients within 3 months of a stroke (66 with CS and 66 with SKC) to undergo 3-week ambulatory cardiac rhythm monitoring using the CardioNet MCOT system. Stroke group was assigned by consensus between two vascular neurologists upon enrollment based on the Causative Classification of Stroke system. Primary endpoint was detection of PAF of any duration independently confirmed by two cardiologists blinded to the stroke group. The groups were well balanced except that patients with CS tended to be older and to have less hypertension and diabetes. Four patients (2 in each group) were excluded because of insufficient stroke evaluation or early discontinuation of monitoring. Episodes of PAF were detected in 16/64 (25%) patients with CS and 9/64 (14%) patients with SKC (p=0.12). Only 5 patients had episodes of PAF lasting &gt; 30 seconds (3 with CS and 2 with SKC). Six of the 9 patients from the SKC group with PAF had small subcortical infarctions; the other 3 had cortical strokes ascribed to artery-to-artery embolism (2 with complex aortic plaques, 1 with severe vertebrobasilar stenosis). In patients under age 65, episodes of PAF were more common in the CS group (22% vs 3; p=0.07) while in patients age 65 or older the rates of detection were very similar (29% in CS vs 28% in SKC; p=0.9). Conclusions: Very short episodes of PAF are relatively common in patients with CS and with SKC, and their pathogenic significance is unclear. However, considering only patients under 65, a greater proportion of cryptogenic stroke patients had PAF, suggesting it might be pathogenic.