Remote Cardiac Monitoring of Higher-Risk Emergency Department Syncope Patients After Discharge - A Pilot Study
Remote Cardiac Monitoring of Higher-Risk Emergency Department Syncope Patients After Discharge - A Pilot Study
2-3% of emergency department (ED) syncope patients suffer arrhythmia/death within 30-days of
 disposition (either as inpatient or at home) and we have recently developed the Canadian
 Syncope Arrhythmia Risk Score (CSARS) to predict these outcomes. Currently, only holter
 monitoring is used and is applied a few days later. New and innovative remote
 (out-of-hospital) external cardiac monitoring technology has made prolonged monitoring
 possible .

 The primary objective is to compare diagnostic yield (identification of arrhythmia that
 requires treatment) for the following two strategies among higher-risk syncope patients
 discharged home from ED: 15-day external cardiac monitoring (intervention arm) versus 48-hour
 Holter monitor (control arm) Methods: The study will be a double-blind RCT comparing two
 different approaches for detecting serious arrhythmias among high-risk ED syncope patients
 who are discharged home. Cardiophone (live monitor) will be used for the intervention arm and
 the Mobile Cardiac Telemetry (MCT) device will be used for the control arm and both devices
 applied prior to ED discharge. For patient safety purposes and to ensure that the patients
 are similar in both arms, all of the study patients will be monitored for 15-days. MCT will
 function as a holter for first 48-hours and this will be used to compare the diagnostic yield
 in the two study arms. After written informed consent, patients will be randomized 1:1 with
 allocation concealed by web-based randomization and stratified based on the total CSARS
 scores. Data collection: patient demographics, medical history, score predictors, device data
 (failure, false alarms, duration worn), patient symptoms and comfort. Primary outcome will be
 diagnostic yield at 15-days in the two study arms and primary analysis will compare the
 diagnostic yield by intention to treat principle controlling for the stratification factor.
 Sample Size: 300 patients per arm (600 total) to detect a 10% difference in diagnostic yield
 between the arms.

 Impact: Our study will increase early identification of patients with serious underlying
 arrhythmia by combining the CSARS risk tool with innovative remote monitoring technology.
Syncope is sudden transient loss of consciousness followed by spontaneous complete recovery;
 it is a very common problem and can be a precursor to sudden death. This study will increase
 the early identification of patients with serious underlying arrhythmia by combining our
 Canadian Syncope Arrhythmia Risk Score (CSARS) with innovative remote (out-of-hospital)
 monitoring technology. Approximately 2-3% of ED syncope patients will suffer arrhythmia or
 die from unknown cause within 30-days of ED disposition (in-patient or outside the hospital).
 It is the concern for occult arrhythmia and its associated mortality that leads to prolonged
 cardiac monitoring in the ED, observation units or by hospitalization; and wide variations in
 investigations and hospitalization. New and innovative technology has made remote monitoring
 feasible for prolonged periods (15-30 days), and is reliable. This technology allows
 arrhythmias to be transmitted live to a central monitoring station automatically based on the
 device algorithm or by the touch of a button when patients are symptomatic. However, lack of
 tools to identify those at risk has limited the use of this new technology to improve patient
 outcomes. The CSARS tool, developed to predict the 30-day risk of arrhythmia/death showed
 that higher-risk (score ≥3) patients have a 17.2% observed risk arrhythmia/death within 15
 days. The aim of this randomized controlled trial (RCT) is to compare the diagnostic yield of
 15-day event monitor to 48-hour holter monitor (usual care) among higher-risk syncope
 patients discharged home at 10 Canadian EDs.

 Context: Currently, only holter monitoring (records all cardiac beats) for 1-2 days is used
 and prolonged monitoring devices are not used for arrhythmia detection. The majority of
 syncope patients are not monitored when symptomatic. Arrhythmias are detected only if evident
 when patients seek care. The investigators recently completed a multicenter prospective
 syncope study and developed the Canadian Syncope Arrhythmia Risk Score (CSARS). Our results
 show that most serious conditions are identified within the first few hours in ED among the
 low and moderate-risk patients while for non low-risk patients the risk of arrhythmia remains
 high up to 15 days indicating the need for prolonged monitoring.

 Previous studies and Rationale: A small randomized study with the old technology that
 required patient activation for arrhythmia capture found higher diagnostic yield than holter;
 but the utility was limited due to patients' inability to activate the device after symptoms.
 Two small studies of unselected syncope patients, one prospective (n=48) and another registry
 analysis (n=92) found a diagnostic yield 30 - 38% with prolonged monitoring for 7-33 days.
 The diagnostic yield of holter is 1-20% based on the risk of enrolled patients. The role of
 prolonged cardiac monitoring among ED syncope patients has not been well studied. Only holter
 monitoring is being currently used, but inconsistently and is applied a few days later. With
 the technological advances, the investigators hypothesize that 15-day monitoring will lead to
 higher diagnostic yield than holter and plan to apply the devices before disposition for
 high-risk patients discharged home.

 Objectives: The primary objective of the REMOSYNC study is to compare diagnostic yield
 (identification of arrhythmia that requires treatment or exclusion of an arrhythmic cause)
 for the following two strategies in higher-risk ED syncope patients discharged home from ED:
 15-day external cardiac event monitoring (intervention arm) versus 48-hour Holter monitoring
 (control arm) Design and Setting: The study will be a multicenter two-arm, double blinded
 randomized controlled trial (RCT) comparing two different approaches for detecting serious
 arrhythmias among high-risk ED syncope patients who are discharged home. Half of the study
 patients will be randomized to 15-day external cardiac monitoring (intervention group) and
 the other half will be assigned to 48-hour Holter monitoring (control group and current
 practice pattern).

 Patient Recruitment: Consecutive patients who fulfill inclusion and do not meet any exclusion
 criteria will be approached for recruitment at the participating EDs and enrolled after
 informed written consent.

 Randomization: Patients will be randomized in a 1:1 ratio to either receive a 15-day event
 monitor Cardiophone (intervention arm) or a 48-hour holter monitoring with the MCT device
 (control arm). Patients will be stratified based on the total CSARS score: 3-4; 5-6; and 7-8
 and allocated using randomly permuted blocks of varying lengths. Allocations will be
 computer-generated by an independent statistician and concealed by having research staff log
 on to a password-protected Electronic Data Capture (EDC) System located within the
 coordinating center website.

 Intervention: Enrolled patients will receive all outpatient investigations except monitoring
 (which will according to the randomization as per the study protocol) as per the discharging
 physician. Based on their allocation, patients will receive either Cardiophone or the MCT
 device prior to discharge home. The allocation will be concealed and the treating physician,
 patient, outcome assessor and the investigator will be blinded to the arm the patient is
 randomized.

 Data Collection: Patient demographics, medical history, CSARS predictors, results of physical
 examination and investigations, and patient disposition will be collected. The following
 device data will be obtained from the central monitoring station: quality of recordings,
 device failure (rhythm not captured during death or when symptomatic), false alarms due to
 artefacts, times of patient activation of cardiophone device due to symptoms, any rhythm
 abnormalities detected during the symptoms, and monitoring reports for patients in both arms.
 Patients will complete a questionnaire during the follow-up visit regarding any serious
 conditions suffered, their comfort and how secure they felt because of the cardiac
 monitoring.

 Post-ED Care of Study Patients: All patients enrolled in the study will be linked to a local
 cardiology group for any urgent and end of study follow-up as needed. Patients will be
 advised to keep a diary of symptoms during the 15-day monitoring period. Patients in the
 cardiophone arm will have the option of transmitting the rhythm when symptomatic and
 symptom-rhythm correlation will be reported. Patients will be advised to return the devices
 and the symptom diary to the local cardiology clinic or the ED research team the next
 business day after the 15-day monitoring period. All monitoring reports will be completed by
 the central monitoring station within 24-hours and sent to the study cardiologist. If serious
 arrhythmias are detected, then the central monitoring station will contact the patient or the
 family member and advise them to call 911 for the patient to be transported to the ED. If
 other arrhythmias are identified, the central monitoring station will provide an interim
 report to the study cardiologist providing care. The study cardiologist will decide the need
 for urgent follow-up and time-frame within which such follow-up should occur. For patients in
 the control arm with MCT device, the central monitoring station will provide reports for
 48-hour holter monitoring on day 3 and another report on day 16 for cardiac monitoring for
 days 3 to 15. Patients in both study arms will be clearly advised to seek care for symptoms
 as usual. All patients will be monitored for the entire 15-days regardless of early
 arrhythmias detected and will have end of study follow-up and further management as deemed
 appropriate by the cardiologist responsible for the care of the patient.

 Duration of Participation and Withdrawal: Patients will be part of the study actively for
 1-year after recruitment. We plan to conduct a 30-day telephone follow-up and 1-year health
 administrative data linkage for serious outcomes related to syncope. Patients will be free to
 withdraw from the study at any time without providing any reason and without any penalty or
 loss of benefits they are entitled and the number of withdrawals will be monitored. However,
 as these monitoring devices will serve to allay fear of arrhythmia or death among patients,
 the investigators expect very few withdrawals. There will be no restrictions on medications
 or procedures during the study period.

 Data Analysis: The primary analysis will be by intent-to-treat and will compare the
 diagnostic yield (arrhythmia detection or exclusion) at the end of 15-days using data from
 15-day monitoring in the intervention arm and the 48-hour holter monitoring. Secondary
 analysis will include a per-protocol analysis. The Cochran-Mantel-Haenszel test will be used
 for the primary outcome, controlling for the stratification factor (CSARS score). The effect
 of the intervention will be expressed as a risk difference with 95% confidence interval.
 Secondary analysis will include multivariable logistic regression to control for potential
 confounders or imbalances between patients in the study arms. Descriptive statistics for
 baseline characteristics, all outcomes, device performance including failure and patient
 centered measures (adherence, comfort and safety feeling). Additional analysis will include
 comparison of arrhythmias detected that did not require treatment between the groups. There
 will no interim analyses for efficacy performed, but the investigators will monitor trial
 safety as detailed in the Data Safety Monitoring Board section.

 Sample Size: Our sample size is 300 patients per arm (600 total) determined to yield 80%
 power to detect an absolute difference of 10% in diagnostic yield between the study arms
 using a chi-squared test at the 5% level of significance assuming a control arm event rate of
 17% and accounting for 5% attrition. A difference of 10% is feasible based on previous
 studies which have reported an 18% increase in diagnostic yield with prolonged monitoring.

 Data Safety Monitoring Board: This independent committee will be comprised of one emergency
 physician, one cardiologist and a biostatistician from outside the participating sites. This
 board will be responsible for safeguarding the interests and safety of trial participants by
 reviewing adverse events including deaths every 6 months during the study period.

 Anticipated Contributions: Our study will be the first to combine risk-stratification and
 innovative technology to decrease morbidity and mortality, and improve healthcare efficiency.
 This study will create new knowledge regarding the role of prolonged live monitoring among
 high-risk syncope patients and application of device prior to ED discharge. As the monitoring
 is live, timely management of potentially life threatening arrhythmias is possible and can be
 applied to syncope patients not at risk for ventricular arrhythmia and hospitalized solely
 for cardiac monitoring. This will represent a paradigm shift as patients can now be monitored
 at home at a very low cost decreasing ED and hospital crowding. These devices will alleviate
 fears of occult arrhythmia and death and will improve patient outcomes.
Inclusion Criteria:

 1. Adult (age ≥18 years) patients with syncope

 2. High-risk as per the Canadian Syncope Arrhythmia Risk Score (score > or =3)and being
 discharged home after ED physician or consultant assessment.

 Exclusion Criteria:

 1. Syncope patients with a score <3

 2. Those who are hospitalized

 3. Previously enrolled.

 4. Loss of consciousness not related to syncope: prolonged loss of consciousness > 5
 minutes

 5. Change in the mental status from baseline

 6. Patients with alcohol intoxication or illicit drug abuse, witnessed obvious seizure;
 or head trauma, i.e. trauma the initial event.