What is the recommended approach for Autonomic Nervous System (ANS) testing?

Recommended Approach for Autonomic Nervous System (ANS) Testing

Autonomic function testing should be performed in a dedicated laboratory by specialists trained in autonomic testing, using beat-to-beat blood pressure monitoring, continuous ECG, and a motorized tilt table in a temperature-controlled environment (21-23°C), with patients fasting for 3 hours and avoiding caffeine, nicotine, and stimulants on the testing day. 1, 2, 3

Essential Testing Environment and Patient Preparation

• Testing must occur in a specialized autonomic function laboratory within cardiology or neurology departments with appropriate equipment including beat-to-beat BP monitoring, ECG monitoring, motorized tilt table, and 24-hour ambulatory BP monitoring devices 1, 2, 4

• Room temperature must be controlled between 21-23°C in a quiet environment to ensure accurate measurements 1, 3, 4

• Patients must fast for 3 hours prior to testing and avoid nicotine, caffeine, theine, or taurine-containing drinks on the examination day 1, 3, 4

• Testing should ideally be performed before noon under well-controlled resting conditions 1

• Avoid testing during acute illness, fever, infection, dehydration, hypoglycemia, or marked hyperglycemia as these conditions invalidate results 3, 4

Core Testing Battery

No single autonomic function test provides comprehensive assessment; different clinical questions require different test batteries. 1, 3, 4

Cardiovagal Function Tests (Parasympathetic Assessment)

• Heart rate variability (HRV) during deep breathing should be recorded for 4-5 minutes during controlled or spontaneous breathing at 15 breaths/minute, with subjects remaining silent during recordings 1, 3

• Valsalva maneuver requires the patient to perform maximally forced expiration for 15 seconds against a closed glottis (40 mmHg resistance) while monitoring beat-to-beat BP and ECG to assess the four hemodynamic phases 1

• Active orthostatism testing evaluates heart rate response to postural change, with POTS defined as HR increase ≥30 bpm (≥40 bpm in teenagers) within 10 minutes of standing without significant BP drop 2

Orthostatic Testing

• Orthostatic vital signs must be measured to detect orthostatic hypotension, defined as systolic BP decrease ≥20 mmHg or diastolic BP decrease ≥10 mmHg within 3 minutes of standing 2

• Extended standing test (10-15 minutes) may be necessary to detect delayed orthostatic hypotension occurring beyond 3 minutes 2

• Head-up tilt table testing can identify reflex syncope, psychogenic pseudosyncope, and POTS patterns when orthostatic testing is inconclusive 1

Advanced Testing Modalities

The Toronto Diabetic Neuropathy Expert Group identifies five most sensitive and specific approaches for cardiovascular autonomic neuropathy evaluation: 1

1. Heart rate variability (HRV) - Time domain measures (RMSSD, SDANN, pNN50) assess parasympathetic activity; frequency domain spectral analysis provides information about both sympathetic (low frequency ~0.1 Hz) and parasympathetic influences 1

2. Baroreflex sensitivity (BRS) - Measures cardiac-vagal response to blood pressure changes using drug-induced, physically-induced, or spontaneous BP fluctuations; recording should be 4-5 minutes with controlled or monitored respiration 1

3. Muscle sympathetic nerve activity (MSNA) - The only method allowing direct continuous measurement of sympathetic nerve traffic and vascular sympathetic arm of baroreflex, but is invasive, time-consuming, and should not be routinely employed for diagnosis 1

4. Plasma catecholamines - Norepinephrine reflects whole-body sympathetic activity; epinephrine reflects adrenal medulla activation 1

5. Heart sympathetic imaging - Nuclear imaging techniques for research purposes 1

Specific Patient Populations Requiring Testing

• Type 1 diabetic patients with disease duration ≥5 years and all Type 2 diabetic patients, especially those with microangiopathic complications 3

• Patients with symptoms of orthostatic or postprandial hypotension, or episodes of unfelt hypoglycemia 3

• Patients with known neurodegenerative diseases, Parkinsonism, or peripheral neuropathies 3, 4

• Patients with prolonged QTc interval (>440 ms) on ECG 3

• Patients with progressive autonomic dysfunction or neuropathic POTS 4

Critical Technical Specifications for HRV Analysis

• Optimal recording time is 4-5 minutes during well-controlled rest; longer times (7 minutes) may be preferable if fast Fourier transform methods are used or if frequent ectopics require editing 1

• Respiration must be recorded in conjunction with beat-to-beat BP; when respiration cannot be recorded, breathing rate should be controlled at 15 breaths/minute 1

• Subjects must not speak during recordings 1

• Age-related reference curves with 95% confidence limits must be obtained for the healthy population using the same methodology and environment 1, 5

• Pre-filtering of data improves agreement between methods and provides more robust BRS estimates 1

Important Caveats and Pitfalls

• All HRV indices are age-dependent, with results declining significantly with increasing age (r = -0.16 to -0.59) 5

• RMSSD, RMSSDb, and E-I difference decrease considerably with increasing heart rate (r = -0.37 to -0.52), making them less suitable for evaluation without heart rate correction 5

• Testing should be performed at least 2 hours after short-acting insulin administration 4

• Consider appropriate wash-out of interfering drugs, particularly diuretics, sympatholytic agents, and psychoactive drugs 4

• Test results must be interpreted with caution in presence of respiratory or cardiovascular diseases, particularly heart failure 4

• Very low HRV (2-4% of total variability) affects interpretation of spectral components due to non-autonomic components in the respiratory range 1

Clinical Implications

• Cardiac autonomic neuropathy is associated with increased risk of perioperative hemodynamic instability, vasopressor requirements, painless myocardial infarction, and sudden death 3

• Decreased global HRV is a strong predictor of increased all-cause cardiac and arrhythmic mortality, particularly in post-MI patients or those with congestive heart failure 6

• If cardiac autonomic neuropathy is detected, 24-hour ambulatory BP monitoring should be performed to identify nocturnal non-dipping patterns 3