Method Article

A Standardized Head-Up Tilt Test Protocol to Assess Cardiovascular Autonomic Dysfunction in Neurodegenerative Diseases

DOI:

10.3791/72496

⸱

August 18th, 2026

 ,  ,  ,  ,  , 
1Department of Neurology, Nagoya University Graduate School of Medicine, 2Department of Clinical Laboratory, Nagoya University Hospital, 3Department of Neurology, Hamamatsu University Hospital

Corresponding Authors: Masashi Suzuki <suzuki.masashi.c9@f.mail.nagoya-u.ac.jp>, Masahisa Katsuno <katsuno.masahisa.i1@f.mail.nagoya-u.ac.jp>

In This Article

Summary

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This protocol aims to provide a standardized and reproducible head-up tilt test to evaluate cardiovascular autonomic dysfunction, particularly orthostatic hypotension, in patients with neurodegenerative diseases, ensuring reliable assessment under controlled testing conditions and with continuous blood pressure monitoring.

Abstract

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Autonomic dysfunction is a common, clinically meaningful feature of neurodegenerative diseases, particularly Parkinson’s disease and multiple system atrophy. Its evaluation is important for differential diagnosis, disease phenotyping, monitoring of disease severity, and prognostic prediction. Among the various manifestations of autonomic dysfunction, cardiovascular symptoms are especially important, with orthostatic hypotension being a hallmark feature. The head-up tilt test is widely used as a standard method for evaluating orthostatic hypotension. In this video article, we present a standardized protocol for the head-up tilt test designed to assess autonomic dysfunction in patients with neurodegenerative diseases.

Although the head-up tilt test is conceptually simple—evaluating blood pressure changes during postural transition from the supine to the upright position—several methodological considerations are required to ensure reliable and reproducible results. These include the influence of the testing environment on autonomic function and the appropriate assessment of continuously fluctuating blood pressure.

This article provides detailed, practical guidance on the implementation of the head-up tilt test, including optimal test timing, control of the testing environment, pre-test dietary conditions, and blood pressure measurement using continuous noninvasive monitoring devices. In addition, we describe key procedural parameters such as tilt table angle, tilt-up speed, and the duration required for blood pressure assessment, as well as essential precautions to ensure patient safety during the examination.

Through these demonstrations, we aim to promote the adoption of a standardized, reproducible head-up tilt test protocol that can be applied consistently across different clinical and research settings. A well-standardized, highly reproducible, and clinically applicable method for evaluating cardiovascular autonomic failure will improve the comparability of results between studies and enhance the assessment of autonomic dysfunction in patients with neurodegenerative diseases.

Introduction

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Autonomic dysfunction is a common and clinically meaningful feature of neurodegenerative diseases, including Parkinson’s disease and multiple system atrophy, and its evaluation plays an important role in differential diagnosis, phenotyping, assessment of disease severity, and prediction of prognosis1,2. Among autonomic manifestations, cardiovascular involvement is of particular clinical importance, with orthostatic hypotension (OH) being a key feature. In patients with neurodegenerative diseases, OH is associated with an increased risk of falls, syncope, and cognitive decline, underscoring the need for accurate and reproducible assessment3,4.

The head‑up tilt test (HUT) is widely used as a standard method for evaluating OH. Based on the temporal profile following postural change, OH is subclassified into initial (immediate) OH, classic OH, and delayed OH. In addition to blood pressure responses, assessment of heart rate changes during HUT allows application of this test to the diagnosis of postural orthostatic tachycardia syndrome (POTS) (Table 1)5,6. Unlike neurogenic orthostatic hypotension, which is commonly associated with neurodegenerative diseases, POTS typically affects younger individuals and is rarely linked to these disorders. Furthermore, analysis of the relationship between heart rate responses and the magnitude of blood pressure reduction provides clinically useful information for distinguishing neurogenic OH from non‑neurogenic OH5,7.

Other methods for evaluating cardiovascular autonomic function include the active standing test (Schellong test), the Valsalva maneuver, and the deep breathing test. The active standing test is particularly useful for assessing orthostatic blood pressure responses, including initial OH, whereas the Valsalva maneuver and deep breathing test primarily assess autonomic function and are more dependent on the subject’s active cooperation and testing conditions.

In contrast, HUT provides a passive and standardized orthostatic challenge, allowing strict control of testing conditions and highly reproducible assessment of cardiovascular autonomic responses. Although HUT is conceptually simple—assessing blood pressure responses during passive transition from the supine to the upright position—several methodological factors must be carefully considered to ensure reliable and reproducible results. These include environmental influences on autonomic function and appropriate interpretation of continuously fluctuating blood pressure signals. Such considerations are particularly important in patients with neurodegenerative diseases, who are often older and susceptible to comorbid conditions and medication-related effects.

In this video article, we present a standardized, practical HUT protocol for evaluating cardiovascular autonomic dysfunction in neurodegenerative diseases. We provide detailed guidance on test timing, control of the testing environment, pre‑test dietary considerations, and continuous noninvasive blood pressure monitoring. Key procedural parameters, including tilt table angle, tilt‑up speed, and the duration of blood pressure monitoring, are described in detail, along with essential precautions to ensure patient safety during the examination.

The active standing test is widely used to assess orthostatic blood pressure responses and is particularly useful for evaluating initial OH5. When a tilt table is not available, it may also serve as an alternative method for assessing OH8,9,10. Although the standing test lacks a strictly standardized protocol, it is closely related to HUT and is widely used in clinical practice. Therefore, its general procedure and interpretation are briefly demonstrated in the latter part of this video article.

Through these demonstrations, we aim to promote adoption of a standardized, reproducible, and clinically applicable HUT protocol that can be implemented consistently across clinical and research settings. Such standardization is expected to improve comparability between studies and to enhance the assessment of cardiovascular autonomic dysfunction in patients with neurodegenerative diseases.

Protocol

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The procedure described in this article represents a standard clinical autonomic function test. No human subjects research was conducted for the purposes of this protocol; therefore, institutional review board approval was not required under institutional guidelines. Written informed consent was obtained from participants for the recording and publication of the procedure. An overview of the HUT protocol is presented as a flowchart in Figure 1.

1. Required equipment

  1. Use a tilt table capable of achieving passive head-up tilt.
  2. Monitor blood pressure continuously using a beat-to-beat noninvasive blood pressure monitoring system whenever available. Use an automated brachial cuff when continuous blood pressure monitoring is unavailable.
    1. For detecting transient blood pressure changes during HUT, perform continuous beat-to-beat blood pressure monitoring using a finger-cuff device based on the volume-clamp method. Because changes in the relative height of the finger cuff with respect to the heart can affect blood pressure measurements during tilt, secure the hand with the finger cuff at heart level using a sling whenever possible. Use height-correction sensors and upper-arm cuff calibration to improve measurement accuracy.
  3. Monitor the electrocardiogram (ECG) continuously during the examination.

2. Test environment and preparation

NOTE: The most important principle regarding test timing, room conditions, dietary restrictions, and medication management is to maintain a standardized protocol within each institution to improve reproducibility.

  1. Ensure that appropriately trained personnel are available throughout the examination. When possible, assign two examiners to respond to sudden hypotension, syncope, or arrhythmias.
  2. To minimize the effects of circadian variation in autonomic function, standardize the start time of the test whenever possible11. When serial examinations are performed, conduct testing at a consistent time of day to improve comparability of results.
    NOTE: Although orthostatic symptoms are often more pronounced in the morning, the timing of testing should be determined according to local clinical practice and scheduling considerations.
  3. Maintain the examination room at a comfortable neutral temperature (approximately 25 °C). Control lighting conditions using a windowless room or blackout curtains. Avoid directing bright lights toward the subject's face. Avoid directing cold airflow from air-conditioning vents toward the subject.
  4. Ensure an adequate fasting period before testing (e.g., overnight fasting, fasting on the morning of the examination, or at least 2 h after a meal)12.
  5. Review all medications before testing. When clinically appropriate, withhold medications that may affect blood pressure or autonomic function. Continue medications when the objective is to evaluate symptoms under usual treatment conditions. Standardize medication management within each institution whenever possible.

NOTE: Representative medication classes that may influence HUT results are summarized in Table 2.

3. Test procedure

  1. Equipment setup.
    1. Place the subject in the supine position on the tilt table (tilt angle 0°). Apply safety belts, when available, to prevent falls.
    2. Initiate continuous blood pressure monitoring. Secure the arm fitted with the finger cuff.
    3. Apply continuous ECG monitoring whenever possible.
  2. Hemodynamic stabilization before tilt-up.
    1. Maintain the subject in the supine position for at least 10 min.
    2. Confirm stabilization of blood pressure and heart rate before tilt-up.
      NOTE: Movement of any limb can influence blood pressure; therefore, subjects should be instructed to minimize body movement during the examination. Emotional stress can also affect blood pressure; verbal interaction should be limited to reassurance and symptom inquiry.
  3. Tilt maneuver.
    1. Raise the tilt table to 60°–70° (occasionally up to 80°) while continuously monitoring blood pressure and heart rate. Complete the tilt-up maneuver smoothly within approximately 10–30 s.
  4. Hemodynamic assessment after tilt-up.
    1. Maintain the upright position for at least 3 min to assess classic OH. Continue monitoring for approximately 5 min during routine assessment.
    2. Extend the upright period to 10–20 min, or up to 40 min when delayed OH is strongly suspected. Maintain the upright position for up to 10 min when evaluating POTS.
    3. Record blood pressure and heart rate continuously throughout the upright period.
  5. Termination of the test.
    1. Return the subject safely to the supine position after the predetermined upright period.
    2. Confirm stabilization of blood pressure and heart rate.
    3. Complete the examination after hemodynamic recovery has been verified.
      NOTE: Even before completion of the planned upright duration, test termination should be considered according to institutional criteria if orthostatic hypotension is confirmed, systolic blood pressure decreases to 70–90 mmHg (or mean arterial pressure <60 mmHg), prodromal symptoms of syncope occur (e.g., pallor, dizziness, nausea), or serious arrhythmias are detected (e.g., sinus pause ≥ 3 s, heart rate < 40 bpm, sustained tachyarrhythmia). Leg elevation or intravenous fluid administration should be provided as needed.
  6. Post‑test precautions
    1. Monitor the subject carefully during transfer from the tilt table.
    2. Observe for hypotension, dizziness, or falls after completion of the test.
    3. Exercise particular caution in subjects with neurodegenerative diseases or those who experienced blood pressure reduction during HUT.

Results

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Representative results
A flowchart for the classification of orthostatic hemodynamic responses during the HUT is shown in Figure 2. Representative changes in blood pressure and heart rate observed in a healthy subject are shown in Figure 3. Schematic illustrations of blood pressure and heart rate responses in OH and POTS are presented in Figure 4.

Figure 3 shows a technically successful recording, characterized by stable beat-to-beat blood pressure and heart rate signals throughout the examination and clear visualization of the hemodynamic responses to head-up tilt. In healthy individuals, blood pressure is generally maintained through compensatory autonomic responses, with a modest increase in heart rate after tilt-up.

Common suboptimal recordings include motion artifacts, transient loss of finger-cuff signals, and inappropriate positioning of the recording arm relative to heart level. These technical issues may obscure orthostatic blood pressure changes and should be recognized and corrected to ensure accurate interpretation of HUT findings.

Determination of baseline blood pressure and heart rate
When continuous blood pressure monitoring is used, baseline blood pressure and heart rate are defined as the mean values over a stable period immediately before the onset of tilt‑up. As hemodynamic stability before tilt‑up is a prerequisite, the exact duration of the baseline period is not critical; however, in practice, either a 1 min interval or an average over approximately 100 consecutive beats immediately before tilt‑up is commonly used. When intermittent measurements with an automated blood pressure cuff are used, the average or median of multiple measurements obtained prior to tilt‑up is defined as the baseline value.

Evaluation of blood pressure responses
During HUT, a sustained reduction in systolic blood pressure (SBP) of ≥20 mmHg or diastolic blood pressure (DBP) of ≥10 mmHg is diagnostic of OH. Because the magnitude of blood pressure reduction is influenced by baseline blood pressure, a decrease in SBP of ≥30 mmHg may be more appropriate for diagnosing OH in patients with supine hypertension13.

In general, the term OH most commonly refers to OH occurring within 3 min of standing (classic OH). Assessment of OH occurring after 3 min of standing (delayed OH) has been reported to facilitate the detection of milder autonomic dysfunction14.

Initial OH is characterized by a transient, rapid decrease in blood pressure immediately after standing, followed by rapid recovery. A reduction of ≥40 mmHg in systolic blood pressure or ≥20 mmHg in diastolic blood pressure within 15 s is commonly used as a diagnostic criterion for initial OH in clinical practice5,15.

For the diagnosis of OH, except for initial OH, persistence of blood pressure reduction is required. However, no strict definition exists regarding the required duration of persistence. This is because, unlike initial OH, blood pressure in OH generally does not recover rapidly once it has decreased and often remains low or continues to decline. Therefore, the key diagnostic consideration is whether hypotension is sustained rather than transient, and defining a specific duration threshold in seconds has limited practical significance. In clinical practice, OH is often diagnosed when blood pressure reduction persists for more than 1 min or continues until the end of the HUT. In some cases, partial recovery of blood pressure may occur; in such situations, reporting both the maximum reduction in blood pressure and its subsequent course (final stabilized value) is useful for interpretation.

Initial OH is defined by a transient decrease in blood pressure occurring immediately after a postural change, typically during active standing and only rarely during head-up tilt, accompanied by symptoms.

Evaluation of heart rate responses
During HUT, evaluation of heart rate responses is as important as blood pressure assessment. Heart rate generally increases with upright posture; however, a sustained increase in heart rate of ≥30 bpm within 10 min of tilt-up, in the absence of orthostatic hypotension, suggests POTS (Table 1). Interpretation of heart rate responses should be made with caution in patients receiving beta-blockers or in those with cardiac pacing devices, as the diagnostic heart rate increase required for POTS may be attenuated.

Diagnosis of neurogenic orthostatic hypotension
Orthostatic hypotension can be classified as non‑neurogenic OH, caused by abnormal plasma distribution or reduced circulating blood volume, and neurogenic OH, caused by nervous system dysfunction. In non‑neurogenic OH, the arterial baroreflex is preserved, resulting in a compensatory increase in heart rate in response to blood pressure reduction. In contrast, in neurogenic OH associated with neurological disease, baroreflex impairment leads to an attenuated heart rate response to hypotension.

Accordingly, a ratio of the increase in heart rate (bpm) to the decrease in systolic blood pressure (mmHg) of <0.5 during HUT has been proposed as a diagnostic indicator of neurogenic OH7. However, in cases of mild autonomic impairment or early‑stage disease, compensatory heart rate responses may still be preserved; therefore, this criterion should be interpreted with caution.

Active standing test (Schellong test)
After standing, blood pressure should be assessed at approximately 30 s and at 1 min intervals thereafter, with measurements continued up to 5–10 min depending on the diagnostic purpose. Continuous blood pressure monitoring, when available, is particularly useful for detecting initial OH. Because blood pressure recovery may occur by 1 min in patients with initial OH, a measurement obtained at approximately 30 s after standing is particularly important to avoid missing this condition. Initial OH is observed predominantly during active standing and only rarely during head-up tilt testing; therefore, the active standing test is considered the preferred method for its evaluation5,16.

If standing is difficult, blood pressure changes from the supine to the seated position may be evaluated; however, the sensitivity for detecting OH is reduced. Interpretation of blood pressure and heart rate changes in the standing test generally follows the same diagnostic criteria as those used for HUT.

figure-results-1
Figure 1: Flowchart of the head-up tilt test protocol. After ≥10 min of supine rest, BP and HR are recorded. The table is tilted to 60–70° over 10–30 s, followed by upright observation to assess OH. The test is terminated if necessary, and the table is returned to the supine position for recovery. Abbreviations: BP = blood pressure; ECG = electrocardiogram; HR = heart rate; OH = orthostatic hypotension; SBP = systolic blood pressure. Please click here to view a larger version of this figure.

figure-results-2
Figure 2: Flowchart for the classification of orthostatic hemodynamic responses. Initial OH is defined by a transient decrease in BP occurring immediately after postural change, accompanied by symptoms. Sustained OH is classified into classic OH and delayed OH according to the timing of BP reduction after tilt-up. Even in the absence of OH, POTS is diagnosed when a sustained increase in HR of ≥30 bpm within 10 min of tilt-up is associated with symptoms of orthostatic intolerance. Abbreviations: BP = blood pressure; DBP = diastolic blood pressure; HR = heart rate; OH = orthostatic hypotension; POTS = postural orthostatic tachycardia syndrome; SBP = systolic blood pressure; ΔHR = change in heart rate; ΔSBP = change in systolic blood pressure. Please click here to view a larger version of this figure.

figure-results-3
Figure 3: Blood pressure and heart rate responses during the head-up tilt test in a healthy subject. Representative changes in BP and HR observed in a healthy subject are shown. (A) Shortly after the start of the resting period, BP and HR show relatively large fluctuations. (B) After confirming stabilization of BP and HR, the head‑up tilt maneuver is initiated. (C) Immediately after tilt-up, SBP typically remains unchanged or shows a mild transient decrease. A compensatory increase in HR subsequently occurs, accompanied by a rise in SBP. Ultimately, in healthy individuals, SBP during head‑up tilt often stabilizes at a level slightly higher than baseline. DBP often shows a mild increase or remains unchanged immediately after tilt-up. (D) When compensatory mechanisms to reduce venous return induced by head‑up tilt are fully activated, BP and HR stabilize at relatively constant levels. As maintaining a strict resting posture becomes difficult during prolonged standing, fluctuations in BP and HR due to body movements are observed in the later phase of the upright position. Abbreviations: BP = blood pressure; DBP = diastolic blood pressure; HR = heart rate; SBP = systolic blood pressure. Please click here to view a larger version of this figure.

figure-results-4
Figure 4: Blood pressure and heart rate responses during the head-up tilt test in orthostatic hypotension and postural orthostatic tachycardia syndrome. This figure summarizes typical changes in SBP and HR during the head‑up tilt test. Representative patterns of initial OH, classic OH, and delayed OH are shown based on the timing and magnitude of SBP reduction, as well as POTS, characterized by an excessive increase in HR without a significant BP decrease. Dashed lines indicate diagnostic thresholds for SBP reduction (–20 mmHg) and HR increase (+30 bpm). For simplicity, DBP changes are not shown. Abbreviations: BP = blood pressure; DBP = diastolic blood pressure; HR = heart rate; OH = orthostatic hypotension; POTS = postural orthostatic tachycardia syndrome; SBP = systolic blood pressure. Please click here to view a larger version of this figure.

ConditionDefinition
Initial (Immediate) Orthostatic Hypotension
(Initial OH)		A transient decrease in blood pressure occurring within 15 s after standing or head-up tilting, accompanied by syncope or prodromal symptoms of syncope.
Classic Orthostatic Hypotension
(Classic OH)		A sustained decrease in systolic blood pressure of ≥20 mmHg or diastolic blood pressure of ≥10 mmHg occurring within 3 min after standing or head-up tilting, with or without symptoms.
Delayed Orthostatic Hypotension
(Delayed OH)		A sustained decrease in systolic blood pressure of ≥20 mmHg or diastolic blood pressure of ≥10 mmHg occurring more than 3 min after standing or head-up tilting.
Orthostatic TachycardiaA sustained increase in heart rate of ≥30 bpm within 10 min after standing or head-up tilting (≥40 bpm in individuals aged 12–19 years).
Orthostatic Intolerance
(OI)		Symptoms such as dizziness, palpitations, weakness, visual blurring, or exercise intolerance occurring upon standing. The presence of orthostatic hypotension, orthostatic tachycardia, or syncope is not required.
Postural Orthostatic Tachycardia Syndrome
(POTS)		Orthostatic tachycardia accompanied by symptoms of orthostatic intolerance, occurring in the absence of sustained orthostatic hypotension.

Table 1: Diagnostic definitions and clinical characteristics of orthostatic syndromes. Orthostatic hypotension is a diagnostic entity defined by a fall in blood pressure upon standing. According to the timing of blood pressure decrease after standing, OH is classified into initial OH, classic OH, and delayed OH. Orthostatic tachycardia refers to a hemodynamic phenomenon defined by an excessive increase in heart rate during orthostasis. Orthostatic intolerance (OI) is a symptom-based syndrome characterized by symptoms during upright posture. Postural orthostatic tachycardia syndrome is a diagnostic condition defined by the coexistence of orthostatic tachycardia and orthostatic intolerance. Abbreviations: OH = orthostatic hypotension; OI = orthostatic intolerance; POTS = postural orthostatic tachycardia syndrome.

Drug classExamplesSuggested withholding period
Antihypertensive agentsACE inhibitors, ARBs, calcium-channel blockers24–48 h
DiureticsFurosemide, spironolactone24–48 h
VasodilatorsNitrates24–48 h
Pressor agentsMidodrine, droxidopa24–48 h
β-blockersBisoprolol, propranolol24–48 h
Antiparkinsonian medicationsLevodopa preparations, dopamine agonistsConsider withholding when clinically feasible
Psychoactive medicationsTricyclic antidepressants, antipsychoticsConsider withholding when clinically feasible

Table 2: Representative medication classes that may influence head-up tilt test results. Representative medication classes that may affect hemodynamic responses during the head-up tilt test are shown. Medication management should be individualized according to the clinical purpose of testing and patient safety. Abbreviations: ACE = angiotensin-converting enzyme; ARB = angiotensin receptor blocker.

Discussion

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In this video article, we aimed to promote the dissemination of a standardized and highly reproducible HUT protocol by providing a comprehensive description of the required equipment, test environment, pre‑test preparation, and practical procedures. To achieve reliable, reproducible HUT results, it is essential that each facility establish a protocol compatible with its clinical environment.

One of the initial challenges in implementing HUT is the availability of appropriate equipment. As described above, passive postural changes can be partially reproduced using an electric bed or similar devices; however, a tilt table is essential for conducting a standardized HUT. In addition, a dedicated examination room that permits safe installation and operation of the tilt table is required. Once a tilt table and an appropriate testing environment have been established, the next consideration is whether continuous blood pressure monitoring can be implemented or whether intermittent automated measurements must be used, which in turn determines subsequent testing conditions.

The HUT itself does not require highly specialized technical skills. Once the tilt table, examination room, and blood pressure measurement method are in place, the test can be implemented relatively easily. Parameters such as the test start time, tilt angle, tilt‑up speed, and upright duration, as well as other environmental conditions, can then be refined iteratively based on feedback from actual test performance to develop a protocol that best suits the characteristics of each facility.

Although the HUT is not technically demanding, attention to patient safety is critical. As discussed in the Protocol section, HUT is a test designed to provoke hypotension and syncope. Therefore, appropriately trained personnel should be available to respond promptly to sudden blood pressure drops, syncope, or arrhythmias. When feasible, two examiners are recommended. Very rapid tilt within a few seconds may introduce emotional stress, stimulate the vestibular system, and increase the risk of vertigo. Conversely, slow tilt over approximately 30 s may be technically difficult with manual tilt tables.

Larger tilt angles increase venous pooling and facilitate the detection of orthostatic hypotension, but they also enhance muscle pump activation, which is undesirable when evaluating baroreflex‑mediated responses. From a safety perspective, lower tilt angles are advantageous, and 60° is generally feasible even in patients with muscle weakness or postural instability, such as those with neurodegenerative diseases. In patients with known severe orthostatic hypotension, testing at 20–30° may be considered.

While this article focuses primarily on HUT in patients with neurodegenerative diseases, HUT should be performed with particular caution in patients with suspected cardiogenic syncope or a history of cardiac disease. When a cardiogenic cause is suspected, consultation with a cardiologist should be considered to determine the appropriateness of HUT and to ensure adequate cardiovascular evaluation before the procedure. Such collaboration may facilitate the safe and appropriate use of HUT in clinical practice.

In patients with neurodegenerative diseases, OH occurs when baroreflex-mediated sympathetic cardiovascular responses fail to compensate adequately for the reduction in cardiac output resulting from decreased venous return during passive upright posture. Consequently, blood pressure usually recovers when the tilt table is returned to the supine position, restoring venous return. In neurodegenerative diseases such as Parkinson’s disease, in which autonomic dysfunction often progresses gradually, blood pressure during HUT commonly declines slowly over tens of seconds. However, in multiple system atrophy or advanced Parkinson’s disease, rapid blood pressure decline may occur immediately after tilt‑up, requiring heightened vigilance.

Several additional factors may indicate a higher risk of OH during HUT. Reduced respiratory‑related heart rate variability during supine rest (i.e., a nearly fixed heart rate with minimal fluctuation) and the presence of supine hypertension may suggest underlying autonomic dysfunction and warrant careful monitoring for hypotension. Similarly, the absence of a compensatory increase in heart rate after tilt‑up, or an excessive heart rate response—possibly reflecting preserved cardiac compensation despite insufficient peripheral vasoconstriction—may be associated with subsequent blood pressure decline. Although a higher baseline blood pressure or the presence of supine hypertension tends to result in a greater absolute reduction in blood pressure after tilt‑up, previous studies have shown that syncope and presyncopal symptoms are more closely related to absolute blood pressure values than to the magnitude of blood pressure reduction itself17.

Troubleshooting
Several technical issues may affect HUT recordings, including motion artifacts, transient loss of finger-cuff signals, and inappropriate arm positioning relative to heart level. These problems may obscure orthostatic blood pressure responses and should be corrected by minimizing body movement, securing the recording arm, and maintaining the finger cuff at heart level throughout the examination.

Limitations
Several limitations of HUT should be recognized. Initial orthostatic hypotension is observed predominantly during active standing and may not be adequately captured during HUT. Furthermore, test results may be influenced by medications, hydration status, environmental conditions, and the availability of continuous blood pressure monitoring. Therefore, interpretation should always be made in the context of the clinical presentation and testing conditions.

Comparison with existing methods
Compared with the active standing test, HUT provides a passive and standardized orthostatic challenge with greater control of testing conditions and improved reproducibility. In contrast, the active standing test is better suited for evaluating initial orthostatic hypotension. The Valsalva maneuver and deep breathing test provide complementary information regarding autonomic function but require greater subject cooperation.

Significance
In summary, this article systematically presents a standardized and practical HUT protocol for evaluating cardiovascular autonomic dysfunction in neurodegenerative diseases. By harmonizing the test environment, pre‑test preparation, equipment settings, tilt parameters, evaluation indices, and safety considerations, the protocol enhances reproducibility and quantitative reliability, enabling meaningful comparisons across institutions and studies.

The HUT is useful not only for identifying classic OH but also for distinguishing initial and delayed OH and for differentiating neurogenic OH based on heart rate responses. Widespread adoption of this standardized HUT protocol is expected to improve diagnostic accuracy and clinical decision‑making, advance understanding of autonomic pathophysiology in neurodegenerative diseases, and provide a robust foundation for future clinical and research studies.

Disclosures

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The authors used an AI-based language model to assist in refining the language and presentation of parts of the manuscript. All content was reviewed and approved by the authors, who take full responsibility for the accuracy and interpretation of the work. The authors declare no other conflicts of interest.

Acknowledgements

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The authors thank the clinical staff for their assistance with HUT and data acquisition. We also thank the participants for their cooperation. This work was supported by JSPS KAKENHI Grant Number JP24K10639 and AMED Grant Number JP 26ek0109863.

Materials

List of materials used in this article
NameCompanyCatalog NumberComments
Continuous blood pressure monitoring deviceMasimo, California, USALiDCOrapid V3 monitor
Electrocardiographic systemFukuda Denshi, Tokyo, JapanFDX-4521Lmodel discontinued; equivalent ECG monitors may be used
Manual or motorized tilt tableManufacturer unknownN/AUsed for passive head-up tilt testing

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