Chapter 71 Head-up Tilt-Table Test
Definition of the Head-up Tilt-Table Test
The head-up tilt-table test (HUTT) is simply a method of subjecting patients to a prolonged upright position. It provokes a range of normal and abnormal responses and is used most commonly to investigate syncope. Tilt tests induce syncope or presyncope in most patients with otherwise undiagnosed syncope and induce the same endpoints in only a minority of control subjects.1 HUTTs have been used in diagnostic studies in populations such as those with neurally mediated syncope (NMS2; “reflex fainting”), syncope in the setting of structural heart disease, and loss of consciousness that might be caused by epilepsy. These tests are also used for the assessment of orthostatic hypotension, autonomic neuropathy, and postural orthostatic tachycardia syndrome.2 They have been used as entry criteria in observational studies and clinical trials, mechanistic physiological studies of the neurally mediated reflex, and in pharmacologic treatment studies and have been proposed to be useful for selecting efficacious treatment.3,4 Tilt tests have made the informed care of syncope patients more accessible and less daunting. By their ability to induce syncope under controlled conditions, they have reassured many patients about a relatively benign diagnosis.
Indications for the Head-up Tilt-Table Test
Syncope is a common problem. Community-based epidemiologic studies have shown that the lifetime prevalence of syncope is over 40% and that many people experience recurrent episodes of fainting.5 The neurally mediated (vasovagal) reflex is the most common cause, particularly in young people, but other causes are also frequently seen. Syncope is responsible for about 1% of emergency room visits and 1% to 3% of hospital admissions, and syncope patients are frequently referred to internists, cardiologists, and neurologists.6 A diagnostic process with reasonably high accuracy was needed to discriminate syncope caused by potentially fatal conditions from syncope caused by more benign ones. In the late 1980s, a number of groups reported the usefulness of the HUTT in diagnosing the particularly common neurally mediated reflex, which is the cause of NMS.7,8 Tilt tests are now widely used for diagnosing syncope, and they have been used as tools for physiological studies, for predicting outcome, and for selecting therapies.
Tilt testing is not the only diagnostic modality that is used for investigating the cause of syncope. Quantitative histories and implantable loop recorders are also under active investigation and are used in clinical practice. The uses of a focused syncope history, tilt tests, and loop recorders are all recommended in clinical guidelines.2 The cause of syncope can be comfortably determined with a good history in most cases, and the need to proceed with tilt testing or loop recorders should be determined on a case-by-case basis. Commonly, tilt tests are used if a clinical suspicion of some form of autonomic disorder such as NMS or an autonomic neuropathy is present, and loop recorders are indicated for a suspected arrhythmia.
Protocols and Procedures of the Head-up Tilt-Table Test
The core of the HUTT is passive head-upright tilt for 20 to 60 minutes until hypotension, bradycardia, and presyncope or syncope ensues or until the test ends. Variants of this method include the use of intravenous isoproterenol, sublingual nitrates, intravenous clomipramine, or combined lower-body negative pressure to induce an endpoint either earlier or with higher likelihood.9–13 Consensus conferences have recommended different uniform protocols, but no formal comparison of their diagnostic accuracies has been made.2 Protocols that use a steeper tilt angle or a longer duration of tilt and drug interventions have higher positive yields and lower specificities.
An example of the tilt testing equipment and protocols at one hospital is outlined in Table 71-1. Patients are studied either after overnight fasting or at least 2 hours after food absorption to decrease the risk of vomiting and aspiration. The patient is placed on a table (that has a footboard), which can rapidly and smoothly incline from a supine position to head-up tilt (between 60 and 80 degrees from baseline) and, more importantly, can rapidly return to the supine position in the event of hypotension or unconsciousness. Restraints are applied to the patient to avoid accidental falls during loss of consciousness. Some centers, but not all, routinely insert an intravenous catheter (after starting electrocardiogram [ECG] monitoring). This allows administration of medications, either for provocation (isoproterenol, nitroglycerin, or clomipramine) or rarely for rescue (saline or atropine). During the test, the ECG values for both heart rhythm and heart rate (HR) and blood pressure (BP) are monitored. While many laboratories measure only arm-cuff BP every 2 to 5 minutes, continuous BP measurements (either with an arterial line or with continuous noninvasive technology) provide more information, especially at the time of hypotension and fainting when an automatic arm cuff can sometimes pose difficulties in documenting BP. Adjunctive investigations can be combined with the HUTT in special circumstances, and some are listed in Table 71-2.
Table 71-1 Vanderbilt Heart Institute: HUTT Lab Protocol
HUTT, Head-uptilt-table test; ECG, electrocardiogram; BP, blood pressure; IV, intravenous; RN, registered nurse; TKVO, to keep vein open; ACLS, Advanced Cardiac Life Support; NPO, nothing by mouth; NS, normal saline; HR, heart rate.
Table 71-2 Adjunctive Investigations During Head-up Tilt-Table Test
Definition of a Positive Head-up Tilt-Table Test
A positive test for NMS requires both the presence of hypotension (usually with relative or absolute bradycardia) and the reproduction of some clinical symptoms before and after the faint. Investigators of the VASIS (Vasovagal Syncope International Study) developed a classification scheme to subcategorize positive hemodynamic responses to the HUTT on the basis of the relative roles of bradycardia and vasodepression (Table 71-3), although the clinical usefulness of the classification is not yet clear. Some patients can have a typical hemodynamic pattern for NMS, but the symptoms are not clinically reminiscent. While these patients may be predisposed to this type of fainting, it may be unrelated to their current clinical problems. The HUTT can also demonstrate patterns of orthostatic tachycardia or orthostatic hypotension (immediate or delayed).
Table 71-3 Revised Vasovagal Syncope International Study (VASIS) Classification of Positive Head-up Tilt-Table Test45
| TYPE 1: MIXED |
| Heart rate falls at the time of syncope, but the ventricular rate does not fall to <40 beats/min or falls to <40 beats/min for less than 10 seconds with or without asystole of <3 seconds. Blood pressure falls before heart rate falls. |
| TYPE 2A: CARDIOINHIBITION WITHOUT ASYSTOLE |
| Heart rate falls to a ventricular rate <40 beats/min for more than 10 seconds, but asystole of more than 3 seconds does not occur. Blood pressure falls before heart rate falls. |
| TYPE 2B: CARDIOINHIBITION WITH ASYSTOLE |
| Asystole occurs for more than 3 seconds. Heart rate fall coincides with or precedes blood pressure fall. |
| TYPE 3: VASODEPRESSOR |
| Heart rate does not fall more than 10% from its peak at the time of syncope. |
Passive Drug-Free Head-up Tilt-Table Test
Protocol
The traditional HUTT protocol involves tilting a subject to at least 60 degrees head-up tilt or more commonly to 70 to 80 degrees head-up tilt for up to 45 minutes’, duration.14–16 Drug-free protocols have reported positive yields of about 50% and specificities of about 90%.1 The primary advantage of these protocols is that only passive orthostatic stress is involved, without the possible confounding effects of a nonphysiological response to a drug.
Isoproterenol and the Head-up Tilt-Table Test
Protocol
After a short drug-free HUTT phase, patients are infused with incremental doses of isoproterenol ranging from 1 to 3 µg/min for 10 minutes at each level of isoproterenol. Doses of 5 µg/min at an angle of more than 80 degres for more than 10 minutes provoke a high rate of false-positive tests. However, using only a 15-minute drug-free HUTT followed by isoproterenol 1 to 3 µg/min has a reported positive test rate of ~60% and specificity greater than 90%.9
Nitroglycerin and the Head-up Tilt-Table Test
Protocol
Intravenous nitroglycerin infusions and sublingual nitroglycerin with tilt testing also provoke the neurally mediated response.10,11 Sublingual nitroglycerin 0.3 to 0.4 mg following a 45-minute drug-free HUTT has a positive test rate for patients with syncope of unknown origin of 61% and a specificity of 94%.2 The advantages of sublingual nitroglycerin over isoproterenol are improved convenience, improved tolerance, and ease of use. Although both isoproterenol HUTT and nitroglycerin HUTT have comparable rates of positive tests and true-negative rates, Oraii et al17 found that 75% of their cases had discordant responses to the two tests, suggesting that the provocative agents may provide complementary information.
Clomipramine and the Head-up Tilt-Table Test
Protocol
Theodorakis et al12 reported that a protocol that included infusing intravenous clomipramine 5 mg over 5 minutes was associated with a total positive response rate (both passive phase and with clomipramine) of 80% and a specificity of more than 95%. The putative mechanism involves an acute increase in synaptic serotonin because of acute serotonin reuptake blockade. This has not been widely used, possibly because of difficulty in obtaining the drug outside Europe.
Physiology Underlying the Head-up Tilt Table Test
Assumption of the upright posture requires prompt physiological adaptation to gravity.18 About 500 mL of blood rapidly descends from the thorax to the lower abdomen, buttocks, and legs. In addition, a 10% to 25% shift of plasma volume out of the vasculature and into the interstitial tissue occurs, mostly within 10 minutes of upright posture, with a slow ongoing shift after that time.19,20 This shift decreases venous return to the heart, resulting in a transient decline in both arterial pressure and cardiac filling. This has the effect of reducing the pressure on the baroreceptors, triggering a compensatory sympathetic activation that results in an increase in HR and systemic vasoconstriction (countering the initial decline in BP). Hence, assumption of upright posture results in a 10 to 20 beats/min increase in HR, a negligible change in systolic BP, and an approximately 5 mm Hg increase in diastolic BP.
The most common pathophysiological explanation for NMS is known as the ventricular hypothesis.21 This hypothesis argues that the initiating event is a pooling of blood in the legs (from prolonged sitting or standing) with a resultant reduction in venous return (preload) to the heart. The resultant decrease in BP leads to a baroreceptor-mediated increase in sympathetic tone. This increased sympathetic tone leads to increased chronotropic and inotropic effects. The vigorous contraction, in the setting of an underfilled ventricle, is thought to stimulate unmyelinated nerve fibers (ventricular afferents) in the left ventricle. This is then thought to trigger a reflex loss of sympathetic tone and an associated vagotonia (with resultant hypotension, bradycardia, or both).
This hypothesis seems to provide a plausible explanation for the postural prodrome to many of the episodes of NMS and provides a rationale for the use of the HUTT. However, even among patients with postural NMS, some experimental observations do not fit completely within this model.21
Accuracy of the Head-up Tilt-Table Test
Gold Standard Populations
Tilt testing has a core problem: It has not been validated against a syndrome that has gold standard diagnostic criteria. In essence, the syndrome is defined by tilt tests rather than being diagnosed by tilt tests. Waxman et al reported that isoproterenol tilt tests induce syncope or presyncope in 75% of subjects with pre-existing classic NMS induced by situations such as the sight of blood or medical procedures.22 However, Agarwal et al reported that of their 12 subjects who developed the neurally mediated reflex during angioplasty sheath withdrawal, none had positive tilt tests.23 Therefore, most reports on tilt tests refer to the proportion of positive studies as positive yield rather than as sensitivity.
Head-up Tilt-Table Test Sensitivity
A positive response was seen in 49% of drug-free HUTTs and 61% to 69% of drug-provoked tests in patients with prior syncope.1,2 It is possible that many patients with NMS may have false-negative tilt tests. Even aggressive tilt protocols using isoproterenol appear to be incompletely sensitive in the case of patients who otherwise are similar to those with positive tilt tests.24
Specificity of the Head-up Tilt-Table Test
Studies of the specificity of tilt tests are equally difficult to interpret. The first lifetime syncopal spell can occur at any age up to about 45 years, and the lifetime prevalence is around 40%.5 This raises several problems. First, how many healthy control subjects are predisposed to faint but have simply not yet fainted? Second, if the HUTT identifies people predisposed to fainting, then populations of younger control subjects will appear to have more false-positive tilt tests. This will confound the studies on aging and the autonomic nervous system. Finally, the specificity of a tilt test protocol seems to be inversely related to its positive yield. Thus a “false-positive” tilt may be a mistake (it may be truly false), or it may reflect a physiological propensity to a neurally mediated reaction that has yet to manifest clinically. No ideal protocol exists, but an optimal compromise appears to have both test positivity and specificity around 70% to 75%.
Effect of Protocol Variability on the Head-up Tilt-Table Test Results
Controlled studies have shown that the likelihood of positive tests depends on whether intravenous cannulation is used, the angle and duration of the HUTT, whether and how a drug challenge is used, the number of head-up iterations during the test, the volume status of the subject, and the subject’s age.2,16,25–33 Outcomes can be quite sensitive to subtle changes in tilt conditions. Protocols that use a longer observation period, a steeper tilt angle, and drug interventions have a higher diagnostic yield and lower specificity. Similarly, younger subjects are more sensitive to tilt testing, whether or not isoproterenol is used. While both isoproterenol and nitroglycerin increase the diagnostic yield of the HUTT by the same proportion, the two provocative agents might select different patients.17
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