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Assoc. Prof Iana Simova
Syncope (transient loss of consciousness due to transient global cerebral hypoperfusion characterized by rapid onset, short duration and spontaneous complete recovery) is a very common condition. Tilt-table testing (TTT) plays a major role during the evaluation of syncope patients, helps to differentiate syncope subtypes and to discriminate between syncope and other common conditions such as epilepsy, and could be useful in guiding treatment. Nevertheless, TTT is still underutilized in many centers, and syncope patients are often subjected to a large number of different diagnostic tests which significantly increase health costs and have little diagnostic yield.
Transient loss of consciousness (TLOC), commonly referred to as fainting, encompasses not only syncope, but also epileptic seizures, psychogenic, and other rare miscellaneous causes. What differentiates syncope from other forms of TLOC is its pathophysiology, including transient global cerebral hypoperfusion due to low peripheral resistances and/or low cardiac output 
Current syncope classification, established by the European Society of Cardiology (ESC), is a pathophysiological one and distinguishes three main categories of syncope: reflex/neurally mediated syncope (vasovagal, situational, carotid sinus syncope and atypical forms), syncope due to orthostatic hypotension (primary or secondary autonomic failure, drug-induced orthostatic hypotension, volume depletion), and cardiac syncope (due to arrhythmia or structural disease) . Based on the recent increase in the ability to document spontaneous syncope episodes, there is also a new classification differentiating syncope in relation to the underlying mechanism: bradycardia, tachycardia and no or slight rhythm variations (hypotension) .
TLOC/syncope is extremely common in the general population with a cumulative incidence of first syncope episode around 10% up to 80 years [1-3]. The outcome of patients with syncope is related more to the severity of the underlying condition rather than to the syncope episode itself. In the absence of structural or electrical heart disease, the prognosis regarding risk of death and life-threatening events is generally excellent , although the risk of syncope recurrences and physical injuries may still persist .
There are different diagnostic tests which should be applied in patients with TLOC, but their main purpose is to provide an answer to two questions: 1) what is the prognosis (regarding death, serious adverse events and recurrences), and 2) what is the specific cause and is there an effective specific treatment strategy [1,2]? Initial assessment includes history, physical examination and ECG, followed by initial risk stratification and additional diagnostic tests if appropriate. These include tilt-table testing (TTT), carotid sinus massage, ECG monitoring (in-hospital, Holter, implantable loop recorders, telemetry), echocardiography, exercise stress testing, electrophysiological study, cardiac catheterization, neurological evaluation (electroencephalography, computed tomography and magnetic resonance imaging, neurovascular studies) and psychiatric evaluation.
Tilt-testing enables the reproduction of reflex syncope in a laboratory setting. Positive responses in patients with neurally mediated syncope are 61-69% and specificity is high (92-94%) . The most commonly used protocol includes tilting to 70°, a passive unmedicated phase of 20 minutes, application of 300-400 μg sublingual nitroglycerine at the 20th minute and an additional 20 minutes of standing .
The most common indication for TTT is to confirm a diagnosis of reflex syncope in patients in whom this diagnosis has been suspected but not confirmed by the initial evaluation . This includes cases with a single unexplained syncope in a high-risk setting or those with multiple recurrent episodes when a cardiovascular cause has been reasonably excluded. TTT is also recommended when it is of clinical value to demonstrate susceptibility to reflex syncope to the patient.
Other indications for tilt-testing are discrimination between reflex syncope and orthostatic hypotension  or falls , between TLOC with jerking movements and epilepsy , and in patients with frequent episodes of TLOC and suspicion of psychiatric problems .
According to the induction of syncope and blood pressure (BP) and heart rate (HR) reaction, there could be several types of response to tilting  – Table 1.
Table 1. Different types of response to tilt-testing.
BP falls to a systolic value <60 mmHg. HR during syncope does not fall by more than 10% of its peak value.
Cardioinhibitory syncope without asystole
HR decreases <40 beats/minute for more than 10 sec, without asystole >3 sec. BP decreases before HR fall.
POTS: postural orthostatic tachycardia syndrome
Compared to other diagnostic tests, TTT, has one of the highest diagnostic yields if the result is abnormal, with the test being diagnostic in more than 50% of cases [11,12]. However, this is the situation which exists in specialized syncope centers and units, where a diagnosis can be established in more than 50% of patients with a mean of three tests per patient [11,12].
There have been concerns that the diagnostic utility of TTT is not high enough, and that a positive TTT rather suggests the presence of hypotensive susceptibility than provides a diagnosis of reflex syncope . However, performing tilt-testing according to ESC guidelines could have a high diagnostic yield (higher than most of the other tests).
Occurrence and recurrence of TLOC could have a major impact on a patient’s wellbeing and social adaptation. Most of the tests initially performed on these patients (mostly in general practices and not in dedicated syncope units) do not yield any positive results. It is still widespread practice to refer such cases to a neurologist who will perform different tests to exclude epilepsy, which can be additionally frustrating for the patient. Generally, these tests have a much lower diagnostic yield compared to tilt-testing. In such a situation the ability to apply a simple and non-invasive test (like TTT) which could confirm the diagnosis of the most common syncope type – reflex syncope – is of great value.
The type of response to tilt-testing could guide patient management. Patients with vasodepressor and mixed syncope and those with orthostatic hypotension most of all need reassurance regarding the benign nature of the condition . Education plays a key role in this setting and includes avoidance of triggering factors, increase in fluid intake, physical counterpressure maneuvers  and tilt-training .
The proper management for patients with cardioinhibitory syncope with asystole has been the subject of much debate. The question here is if pacing would reduce syncope recurrences. Several randomized controlled trials based on tilt-testing response have given conflicting results [16-19]. The International Study on Syncope of Uncertain Etiology (ISSUE)-2 study showed a striking reduction in the recurrence of syncope with pacing in patients with documented asystole during spontaneous syncope (implantable loop recorder monitoring) . ISSUE-2 was a non-randomized trial, but recently its results were confirmed by the randomized ISSUE-3 .
At present, the issue regarding the appropriateness of pacing patients with TTT-induced asystole during syncope is not fully resolved. The decision to implant a pacemaker (an invasive procedure) should be taken in the clinical context of a benign (in terms of mortality) condition that usually affects young individuals and often children. My personal experience (including children) is to refer patients with TTT-induced asystole during syncope to pacing only as a last resort and in cases of profound asystole (>6 sec) [22,23].
Associate Professor Iana Simova, MD, PhD
Department of Noninvasive Cardiovascular Imaging and Functional Diagnostics, National Cardiology Hospital, Sofia, Bulgaria
Author’s disclosures: No conflicts of interest to declare.