Diagnostic Yield of an Ambulatory Patch Monitor in Unexplained Emergency Department Syncope: A Pilot Study (PATCH-ED)
Diagnostic Yield of an Ambulatory Patch Monitor in Unexplained Emergency Department Syncope: A Pilot Study (PATCH-ED)
Syncope is a common Emergency Department (ED) presentation but the underlying diagnosis is
 not apparent in 60% of patients after assessment and serious adverse event rate is 7% at one
 month with most having acute cardiovascular events, also more likely to be unexplained after
 ED assessment. Many cardiovascular events are due to arrhythmia, difficult for clinicians to
 diagnose, as examination and Electrocardiogram (ECG) findings may both be normal and symptoms
 have resolved by the time the patient gets to the ED. Currently establishing a cardiac
 arrhythmia as the cause of syncope rests on correlating the arrhythmia with symptoms using
 monitoring devices such as Holter but these all have significant drawbacks. The clinical
 challenge in the ED is therefore to identify the moderate and high-risk patients and refer
 them for further investigation and monitoring if appropriate. The logistics of arranging
 follow up within a timely period of the patient's ED visit is often problematic for a variety
 of reasons including availability of timely specialty outpatient appointments, a lack of
 consensus of the specialty to whom the syncope patient should be referred (cardiology,
 medicine, neurology, general practice) and availability of Holter and other monitoring
 devices. For this reason most high and medium risk patients are admitted to hospital.

 Previous syncope clinical decision rules have not been well adopted due to their lack of
 sensitivity and specificity probably due to the varied and heterogeneous nature of
 potentially serious causes. However, the majority of patients with syncope have no serious
 underlying pathology and do not require hospitalisation. Rather than continued attempts at
 risk stratification of outcome based on presentation, more research is required into how we
 can better improve diagnosis and therefore treatment in order to provide improved patient
 benefit. We believe that ambulatory patch monitoring will allow better and earlier arrhythmia
 detection and plan to assess the ability of a 14-day ambulatory patch to detect serious
 arrhythmic outcomes at 90 days.
There are around 650,000 ED syncope presentations a year in the United Kingdom (UK). Serious
 underlying conditions can present with syncope and one-month serious adverse outcome is
 around 7% with 50% being cardiovascular. The treating ED clinician is not always able to rule
 out serious pathology as the patient is commonly fully recovered on arrival in the ED,
 despite the underlying cause being potentially life threatening should it recur again. Whilst
 most patients do not have a serious underlying cause and therefore do not require
 hospitalisation, the concern of the ED clinician about missing a serious underlying cause
 (especially cardiovascular ones) means that 50% of syncope patients are admitted to hospital.

 Despite research identifying high-risk demographic, historical and examination variables,
 clinical decision rules have not been well adopted due to their lack of sensitivity and
 specificity probably due to the varied and heterogeneous nature of potentially serious
 causes. Rather than continued attempts at risk stratification of outcome based on
 presentation, more research is required into how we can better improve diagnosis and
 therefore treatment in order to provide improved patient benefit.

 Cardiovascular causes of syncope fall into two main categories, arrhythmia (e.g. ventricular
 tachycardia (VT), 2nd degree Mobitz II, 3rd degree atrioventricular block or symptomatic
 bradycardia) and structural (e.g. aortic stenosis). It is arrhythmia that is most difficult
 for the ED clinician to diagnose in the ED as examination and presenting Electrocardiogram
 ECG may both be normal. It is for this reason that arrhythmia makes up a large number of
 subsequent serious outcomes in syncope patients whose syncopal cause is unexplained after ED
 assessment.

 The current main method for establishing a cardiac arrhythmia as the cause of syncope rests
 on the correlation of the arrhythmia with symptoms (which will have resolved by the time the
 patient gets to the ED). The clinical challenge in the ED is therefore to identify the
 moderate and high-risk patients and refer them for further investigation and monitoring if
 appropriate. The logistics of arranging follow up within a timely period of the patient's ED
 visit is often problematic for a variety of reasons including availability of timely
 specialty outpatient appointments, a lack of consensus of the specialty to whom the syncope
 patient should be referred (cardiology, medicine, neurology, general practice) and
 availability of Holter and other monitoring devices. For this reason most high and medium
 risk patients are admitted to hospital.

 The investigation of cardiac arrhythmias is usually initiated with the Holter monitor which
 uses a continuous recording over a 24 or 48-hour period. The Holter allows detection of
 baseline rhythm, arrhythmia and conduction abnormalities. Holters however are bulky and
 inconvenient for the patient to wear, the transmission of data is not patient dependent and
 non-compliance with both device use and maintaining a written symptom log, limits its
 diagnostic utility. The lack of extended monitoring reduces diagnostic yield to typically
 less than 20%. Bass reported a diagnostic yield of 15% with 24-hour Holter monitoring that
 did not increase even if the device was applied for 72 hours.

 For these reasons, the use of Holter monitors is not universal in medium and high-risk
 syncope patients. In one UK ED study, only 158 of 540 (29%) admitted syncope patients
 underwent 24 hour monitoring (which in the majority comprised ward telemetry rather than
 Holter). There are other devices available to the Cardiologist to investigate syncope
 patients who are classified as European Society of Cardiology (ESC) medium and high-risk and
 whose Holter investigation is unrevealing. Event recorders do not record a continuous ECG but
 require patient activation at the time of symptoms and must be applied to the chest wall at
 the time of the event and must be activated by the patient. A brief, typically 90-second,
 single lead ECG recording is captured and stored. Because of limited data storage capability,
 data must be transmitted to a monitoring centre for validation and analysis. Event recorders
 can be used for cardiac monitoring over longer periods of time but the big drawback is that
 they must be activated following symptom onset, which may be difficult to achieve if the
 patient has suffered syncope or an injury related to the event. Finally, these devices cannot
 be used to document asymptomatic arrhythmias.

 External continuous loop recorders are attached to the patient by chest electrodes or a
 wristband. They continuously record the ECG but only save data if activated by the patient.
 The continuous looping memory feature allows the device to store a fixed length of
 pre-activation and post-event ECG data. Mobile cardiac telemetry systems provide up to 30
 days of real-time continuous cardiac monitoring without the need for patient activation or
 data transmission. These devices are expensive, require electrodes and bulky recording
 devices, and produce a large amount of data, which requires sifting. Implantable loop
 recorders are surgically implanted subcutaneous devices that continuously record single-lead
 ECG signal through 2 electrodes. They are very expensive and necessitate an invasive surgical
 procedure. For patients admitted to hospital and who are placed on telemetry, there is also
 lack of consensus on the optimal duration of monitoring. Typically higher risk patients are
 monitored for 24 hours and discharged without a diagnosis if their ECG tracing has been
 uneventful during this time period.

 In order to solve these problems, a novel ambulatory cardiac monitoring device that can
 easily be applied to ED patients has recently been developed. The ZIO®XT Patch (iRhythm
 Technologies, Inc. San Francisco, California; http://www.irhythmtech.com/zio-services.php) is
 non-invasive, water-resistant, has no leads or wires, is discrete to wear and has been
 approved for clinical use in the UK. It continuously monitors the heart for up to 14 days
 including during sleep, in the shower, and during moderate exercise and has a large button on
 top for patients to capture symptomatic events. When patients reach the end of their
 monitoring period, they simply mail the device back to the company where analysis is
 undertaken.

 The ZIO®XT Patch is well tolerated for prolonged monitoring and compliance is excellent with
 studies demonstrating a mean monitoring wear time of 10.8 days (range 4-14 days) and 10.9
 days (median 13.0 days). Barrett et al showed that 80% of patients who had worn a Holter
 monitor for 24 hours, and a ZIO®XT Patch for up to 14 days, preferred the ZIO Patch. Single
 channel ECG data quality is also excellent with one study showing more than 98% of the total
 recording time was analysable, and a second study showing a median analysable time of 99% of
 the total wear time. Compliance with returning the device is also good. In a study of 174 ED
 with indications for monitoring (syncope, dizziness and palpitations), all patients mailed
 back their devices.

 Several studies have shown that ZIO®XT Patch has a higher diagnostic yield for arrhythmias
 than traditional 24-48 hour Holter monitoring and importantly can also efficiently
 characterise symptomatic patients without significant arrhythmia. The absence of an
 arrhythmia during syncope, palpitations or a triggered event does not by itself provide a
 definitive diagnosis but does allow the clinician to exclude an arrhythmia as a potential
 cause and is thus clinically useful. Over half of patients (53.4%) in one study did not have
 an arrhythmia despite a triggered event. This allows the clinician to potentially exclude an
 arrhythmia as an etiology of the patient's symptoms and potentially avoid further cardiac
 evaluation.

 Camm et al showed in a study on patients with arrhythmogenic right ventricular dysplasia
 (ARVD), that over the total wear time of both devices, the ZIO®XT Patch detected more
 premature ventricular contraction events than a 24 hour Holter monitor. Barrett et al showed
 ZIO®XT Patch had a 57% greater diagnostic yield than a 24 hour Holter monitor, and Schreiber
 at al demonstrated an overall diagnostic yield of 63% in ED patients with indications for
 monitoring. This study also showed that 48% of patients had ≥1 arrhythmia and 10% were
 symptomatic at the time of their arrhythmia. Median time to first arrhythmia was 1.0 days
 (IQR 0.2-2.8) and median time to first symptomatic arrhythmia was 1.5 days (IQR 0.4-6.7). 54%
 of symptomatic patients did not have any arrhythmia during their triggered events.

 In a study looking at ZIO®XT Patch use in outpatients with clinical indications for
 monitoring (15% of whom had syncope), of the 60% of patients who had an arrhythmia detected,
 30% had their first arrhythmia and 51% had their first symptom-triggered arrhythmia occur
 after the initial 48-hour period. Mean time to first arrhythmia was 1.7 days (median 0.8) and
 mean time to first symptomatic arrhythmia was 3.0 days (median 2.1).

 This novel ambulatory cardiac monitoring device should allow much earlier arrhythmia
 detection in more patients allowing better diagnosis and subsequent treatment.
Inclusion Criteria:

 -  Patients aged 16 years or over presenting within 6 hours of an episode of syncope and
 whose syncope remains unexplained after ED assessment. Syncope will be defined as a
 transient loss of consciousness (TLOC) with inability to maintain postural tone and
 immediate complete spontaneous recovery without medical intervention (to preexisting
 mental status and neurologic function)

 Exclusion Criteria:

 -  Obvious underlying cause after ED assessment,

 -  Alcohol or illicit drugs as presumptive cause of TLOC [24],

 -  Epileptic seizure as presumptive cause of TLOC (seizure activity with a >15 min
 witness reported post-ictal phase) [24],

 -  Stroke ⁄ transient ischemic attack as presumptive cause of TLOC [24],

 -  Head trauma followed by TLOC [24],

 -  Hypoglycemia as presumptive cause of TLOC [24],

 -  No consent i.e. patient lacking capacity,

 -  Previous recruitment into the study,

 -  Patient in custody or prison.

 Obvious underlying causes will be defined as:

 -  Clinical history of vasovagal syncope i.e. pre-syncope symptoms and low-risk patient
 according to current ESC guidelines [14],

 -  Arrhythmia on ED ECG thought to have caused syncope,

 -  Arrhythmia on pre-hospital ECG causing syncope,

 -  Pulmonary embolism (PE) diagnosed on Computed Tomography Pulmonary Angiography (CTPA;
 or equivalent e.g. symptoms of PE plus positive leg ultrasound
 scan/ventilation-perfusion scan/echo),

 -  Postural hypotension (postural drop >20 mmHg in ED with symptoms during test and
 suggestive history),

 -  Myocardial Infarction [25],

 -  CT brain or clinical signs/symptoms in ED showing cerebrovascular accident or
 subarachnoid haemorrhage,

 -  Evidence of haemorrhage in ED thought to have caused syncope,

 -  Other obvious cause of syncope apparent in ED.