Syncope Trial to Understand Tilt Testing Early or Recorders Study
Syncope Trial to Understand Tilt Testing Early or Recorders Study
Pragmatic research study to determine which of the two standard syncope therapies yields a
 faster path to diagnosis- head up tilt (HUT) table or implantable loop recorder (ILR).
RESEARCH QUESTION: In syncope patients at least 50 years of age, a strategy of first
 conducting a tilt table (HUT) will provide an earlier diagnosis at less cost than a strategy
 of first implanting an implantable loop recorder (ILR).

 BACKGROUND: Syncope is a common condition. Approximately 0.6%- 1.5% of all Emergency
 Department (ED) visits occurs for syncope and of these, anywhere from 12%-83% are admitted,
 depending on the country. The incidence rates for acute care visits increases with age and
 rises steeply after the age of 50 years. Approximately one third of patients have at least
 one recurrence of syncope in 3 years of follow-up. A recent analysis from Alberta found the
 total cost of syncope presentations to the ED was $530 million dollars over a 6-year period.
 Syncope has numerous causes, ranging from benign to life threatening, and determining the
 underlying etiology is often challenging. Reflex syncope (vasovagal) is the most frequent
 cause of syncope in all age groups and clinical settings. However, arrhythmic causes, with
 higher clinical risk, become more common in older patients, and are responsible for about 10%
 of syncope visits to the ED. The current approach for investigation of patients with
 unexplained syncope is usually unstructured, with multiple specialist evaluations, numerous
 and expensive tests, and recurring acute care visits. This results in high and unnecessary
 costs. There are three competing approaches to diagnosis: a structured history, head-up tilt
 (HUT) test, and implantable loop recorders (ILR).

 Often syncope can be diagnosed on the basis of history, physical examination, and
 electrocardiogram (ECG). However, even after this initial evaluation, syncope may remain
 unexplained, accounting for as many as 41% of cases in older patients. In older patients,
 history is often less reliable, due to a lack of autonomic symptoms associated with vasovagal
 syncope, amnesia for pre-syncopal symptoms, and lack of witnesses. Further, co-morbidities
 and polypharmacy add complexity to the diagnostic process. HUT: The HUT test has been used to
 evaluate patients with syncope for nearly 3 decades. It is an orthostatic stress test to
 assess the susceptibility of a vasovagal response to a postural change from a supine to an
 upright position. A positive response is defined as inducible presyncope or syncope
 associated with hypotension, with or without bradycardia (including asystole) that reproduces
 clinical symptoms. HUT has been used in patients with suspected vasovagal syncope, when the
 history is unhelpful. Although enthusiasm has waned for the role of HUT in the evaluation of
 syncope due to variable protocols leading to high heterogeneity of test outcomes,
 false-positives in controls, and availability of long-term cardiac monitoring; there is good
 evidence for its usefulness.

 ILR is a small subcutaneously implanted device, lasting up to 3 years, that records heart
 rhythms, and which may be either auto-triggered or patientactivated.

 Early observational and case-control studies found that the ILR leads to earlier diagnosis
 and reduced the rate of unexplained syncope compared to HUT. Despite ILR entering routine
 clinic practice over the last 25 years, there are surprisingly few rigorous data of its use
 in the management of unexplained syncope. Comparisons of strategies of HUT and ILR: Two
 randomized controlled studies have reported on the diagnostic yield of an early ILR strategy
 compared to conventional testing including HUT in older patients with unexplained syncope.
 All reported an increased diagnostic accuracy with ILR and a lower cost per diagnosis, but
 each has substantial limitations. Study Structure: This will be a formal pragmatic study of 2
 diagnostic strategies, designed around the PRECIS2 criteria addressing which test should be
 done first, and subsequent care will be left in the hands of the physician responsible for
 assessing syncope. Settings: Patients will be recruited from the ED, general cardiology,
 arrhythmia, and syncope clinics, and medical and cardiology wards.

 Randomization: Patients will be randomized to either i) the early HUT [protocol:

 supine pre-tilt phase 5 min, un-medicated HUT to 70 degrees for 20 minutes; if response
 negative then 400 μg of sublingual nitroglycerin and continued 70 degree tilt for 20 minutes]
 OR ii) early implant of ILR without hospital admission.

 Regardless of the outcome, subsequent testing and care will be in the hands of the
 responsible physician. Patients will be seen 1 week after ILR implantation for wound
 assessment and to reinforce patient understanding of the activation process. Subsequent
 3-year follow-up will occur according to the policies of the device clinic (usually every 6
 months). Patients will be seen quickly after a symptomatic event.
Inclusion Criteria:

 -  50 years old

 -  syncope (defined in 2017 ACC/AHA/HRS guidelines[16]) in the prior 12 months

 -  diagnosis unclear after history, physical exam andelectrocardiogram

 -  no apparent risk of death due to the cause of syncope.

 Exclusion Criteria:

 -  inability to give informed consent

 -  unable to attend routine follow up in device clinic

 -  positive carotid sinus massage.