These disorders are usually not associated with underlying structural heart disease. Therefore, in a patient (especially in a younger patient) with a normal ECG and no structural heart disease, one of the disorders of autonomic function should be strongly considered. The most common disorder of autonomic function is neurally-mediated syncope, which includes vasovagal and carotid sinus syncope. Additionally, micturition, defecation, deglutition, and cough (posttussive) are common “situational” forms of neurally-mediated syncope. In these conditions, syncope results from bradycardia and/or hypotension. It is important to note that in many patients with carotid sinus hypersensitivity the hemodynamic alterations may be manifest only in the upright state and that in nearly a third of patients the major hemodynamic effect is a pure vasodepressor response. Therefore, in diagnosing carotid sinus hypersensitivity, patients should be evaluated while supine and upright with use of one of several commercially available devices capable of recording beat-to-beat blood pressure noninvasively.

Chronic orthostatic intolerance, formerly referred to as the postural orthostatic tachycardia syndrome, is characterized by pronounced orthostatic tachycardia without associated hypotension. By definition, the orthostatic symptoms are long-standing (≥6 months) and not attributable to an underlying cause such as a debilitating disease, substantial weight loss, prolonged bed rest, peripheral neuropathy, and/or medications. This is a disorder of the young (age 14 to 45 years) with a female predominance (4:1). The disorder may follow a viral illness in 30% to 40% of cases. The predominant symptoms include light-headedness, dizziness, palpitations, chest pain, and syncope. In some patients, this condition is related to a defect in the norepinephrine transporter, which results in an increase in the norepinephrine concentration. In the upright state, the heart rate increases by ≥30 bpm (usually to an absolute rate ≥120 bpm); upright norepinephrine levels characteristically exceed 600 pg/mL.

Although most commonly a result of volume depletion, orthostatic hypotension may represent a sign of generalized autonomic dysfunction. An identifiable cause is often present such as a systemic disease (e.g., diabetes mellitus), toxic agents (e.g., alcohol), or use of a vasoactive medication. Often a cause cannot be identified; in these instances, one must consider pure autonomic failure (when other neurologic features are absent) or multiple system atrophy (associated with other neurologic features).

Tilt table testing is useful in differentiating these syndromes. In neurally-mediated syncope, in response to upright tilt, the heart rate and blood pressure initially remain stable. However, there is then an abrupt decline in the heart rate and/or blood pressure, which results in syncope. In contrast, patients with chronic orthostatic intolerance have an immediate increase in heart rate (≥30 bpm to ≥120 bpm) without a change in blood pressure, and patients with orthostatic hypotension due to autonomic
dysfunction exhibit a progressive decline in blood pressure (≥20 mm Hg) without a change in heart rate. Figure 5-2 summarizes an approach to the clinical incorporation of tilt table testing when a disorder of autonomic function is suspected.

Although tilt testing is widely used to evaluate patients with suspected neurally-mediated syncope, there is no standardized tilt test protocol. Current practice guidelines advocate that tilt testing be performed in a quiet room with dim lighting. The patient should be fasting for at least 2 h prior to the test. Ideally, patients should be supine for 20 to 45 min (especially when venous cannulation is performed) prior to upright tilt; however, in practice this is quite difficult. Heart rate and blood pressure should be monitored continuously on a beat-to-beat basis. A tilt table with a footboard is essential. Finally, the patient should be tilted to 60 to 70 degrees; tilting to 80 degrees reduces the specificity of the test protocol.

Currently used protocols usually consist of an initial drug-free tilt phase (usually at least 20 min and up to 40 min) followed by a phase using pharmacologic provocation, most commonly with isoproterenol, nitroglycerin, or adenosine. Isoproterenol is infused at a rate of 1 to 3 µg/min in order to increase the resting heart rate by 20% to 25%. Nitroglycerin is typically administered as a 400-µg sublingual spray. At our institution, we do not perform nitroglycerin tilt testing because of concerns over test specificity. Rather, we routinely use adenosine to facilitate the induction of neurally-mediated syncope. Adenosine, like isoproterenol, has sympathomimetic effects, which are mediated through baroreflex and chemoreceptor activation. Single-stage adenosine tilt testing has a diagnostic yield comparable to a two-stage test protocol using drug-free and isoproterenol tilt stages. An attractive feature of adenosine tilt testing is that it takes only 3 min to complete (Fig. 5-3).

Irrespective, the major problem with tilt testing remains its poor sensitivity when using a protocol that maintains high specificity. This limitation is acknowledged in

the most recent AHA/ACC scientific statement on the evaluation of syncope. In patients without structural heart disease, the pretest probability that the diagnosis is neurally-mediated syncope is high, irrespective of the tilt test result. Therefore, it is generally more important to exclude the possibility of serious bradyarrhythmia or tachyarrhythmia as the etiology for syncope. In addition, the sensitivity of tilt testing worsens significantly as the patient population being evaluated becomes older. Furthermore, prospective studies have demonstrated that in patients without structural heart disease who present with syncope, the clinical outcome is similar irrespective of the tilt test response. As a result, the clinical role for tilt testing remains controversial. Finally, a structured approach to obtaining a history in patients with unexplained syncope (e.g., Calgary Syncope Symptom Score) may be far more valuable than tilt table testing to diagnose neurally-mediated syncope.