# Autonomic Disorders and Syncope

## Syncope: Definition and Classification

### Definition

Syncope is defined as a transient loss of consciousness due to transient global cerebral hypoperfusion, characterized by rapid onset, short duration typically lasting less than 20 seconds, and spontaneous complete recovery. The critical diagnostic task is distinguishing true syncope from non-syncopal causes of transient loss of consciousness, including seizure, metabolic derangements such as hypoglycemia, psychogenic pseudosyncope, and transient ischemic attack, which rarely causes loss of consciousness without accompanying focal neurologic deficits.

### Syncope Classification and Key Features

| Category | Proportion | Subtypes | Key Diagnostic Clues | Prognosis |
|---|---|---|---|---|
| Reflex (neurally mediated) | 60-70% | Vasovagal, situational, carotid sinus hypersensitivity | Prodrome (nausea, diaphoresis, warmth); triggers (pain, standing, heat); rapid recovery | Benign |
| Orthostatic hypotension | 10-15% | Neurogenic (autonomic failure), non-neurogenic (drugs, dehydration) | Positional; SBP drop >=20 mmHg within 3 min of standing | Depends on cause |
| Cardiac | 10-15% | Arrhythmic (brady/tachy), structural (AS, HCM, PE, tamponade) | Exertional; supine; no prodrome; palpitations; abnormal ECG; family hx SCD | Potentially life-threatening |

### Classification

Syncope is classified into three major categories based on pathophysiology. Reflex or neurally mediated syncope is the most common cause, accounting for approximately 60 to 70% of cases, and encompasses vasovagal syncope, situational syncope triggered by specific physiologic events, and carotid sinus hypersensitivity. Orthostatic hypotension-mediated syncope results from autonomic failure, drug effects, or volume depletion. Cardiac syncope is caused by arrhythmias, both bradycardic and tachycardic, or structural heart disease such as aortic stenosis, hypertrophic cardiomyopathy, pulmonary embolism, or cardiac tamponade.

## Initial Evaluation

### History -- The Most Important Diagnostic Tool

A meticulously obtained history from both the patient and witnesses is the most powerful diagnostic tool in syncope evaluation, correctly identifying the cause in up to 50% of cases without any additional testing. The circumstances surrounding the event should be explored in detail, including position at the time of onset, activity such as exertion, post-exercise, micturition, defecation, coughing, or swallowing, and identifiable triggers including pain, fear, blood exposure, prolonged standing, hot environments, or crowded spaces.

The nature of the prodrome provides critical diagnostic information. Diaphoresis, nausea, warmth, pallor, tunnel vision, and lightheadedness suggest a vagal mechanism. Preceding palpitations suggest an arrhythmic etiology. Absence of any prodrome raises concern for a cardiac cause with sudden loss of output. Witnessed accounts are invaluable: the duration of loss of consciousness, associated movements where brief myoclonic jerks are acceptable in syncope but tonic-clonic activity lasting more than 30 seconds suggests seizure, skin color with pallor in syncope versus cyanosis in seizure, and post-event confusion that is prolonged in seizure but associated with rapid recovery in syncope all help differentiate the diagnosis. Cardiac red flags that mandate further evaluation include exertional syncope, syncope while supine, preceding palpitations, family history of sudden cardiac death before age 40, known structural heart disease, and an abnormal electrocardiogram.

### Physical Examination

The physical examination begins with orthostatic vital signs, measured with the patient supine for 5 minutes and then immediately after standing and again at 3 minutes. A positive result is defined by a systolic blood pressure drop of 20 mmHg or greater or a diastolic blood pressure drop of 10 mmHg or greater within 3 minutes of standing. Cardiac auscultation evaluates for murmurs suggesting aortic stenosis or hypertrophic cardiomyopathy, with dynamic murmur assessment during Valsalva for the latter, as well as S3 or S4 gallops and irregular rhythm.

Carotid sinus massage is performed in patients over 40 years with unexplained syncope, but is contraindicated in those with a carotid bruit, prior stroke or transient ischemic attack within 3 months, or carotid stenosis exceeding 70%. A positive response is defined as asystole exceeding 3 seconds representing a cardioinhibitory response, or a systolic blood pressure drop exceeding 50 mmHg representing a vasodepressor response, accompanied by reproduction of the patient's clinical symptoms. Neurological examination rules out focal deficits and assesses for signs of autonomic dysfunction.

### ECG -- Mandatory in All Syncope

An electrocardiogram is mandatory in every patient presenting with syncope. Certain findings are diagnostic or highly suggestive of a specific etiology, including sinus bradycardia below 40 beats per minute, atrioventricular block of Mobitz II or complete type, alternating left and right bundle branch block, rapid supraventricular or ventricular tachycardia, prolonged QT interval with QTc exceeding 500 milliseconds, Brugada Type 1 pattern, epsilon waves suggesting arrhythmogenic right ventricular cardiomyopathy, Wolff-Parkinson-White preexcitation, and pacemaker malfunction. Other findings that are suggestive but require further evaluation include bifascicular block, sinus bradycardia of 40 to 50 beats per minute, unexplained left ventricular hypertrophy, Q waves suggesting prior myocardial infarction, short QT interval, and atrial flutter or fibrillation with slow ventricular response.

### Risk Stratification

High-risk features warranting inpatient evaluation include an abnormal electrocardiogram, history of structural heart disease, heart failure, syncope during exertion, syncope while supine, preceding palpitations, family history of sudden cardiac death, severe anemia, and electrolyte abnormalities. Low-risk features include young age, typical vasovagal triggers, long prodrome, postural association, absence of heart disease, and normal electrocardiogram. Validated risk stratification tools including the EGSYS score, Canadian Syncope Risk Score, and San Francisco Syncope Rule assist in emergency department decision-making.

<image>
A diagnostic algorithm for syncope evaluation. Start with "Syncope - Transient LOC with Rapid Complete Recovery" at top. Step 1: "Initial Evaluation: History, Physical Exam (including orthostatic vitals), 12-lead ECG." Three main branches based on diagnosis. Branch 1 (left, green): "Diagnosis Established" → Vasovagal (typical history + prodrome), Situational (micturition, cough, defecation), Orthostatic (positive orthostatic vitals), Classic CSH (positive CSM). → "Treat cause; no further cardiac workup needed." Branch 2 (center, yellow): "Suspected Cardiac Syncope" (abnormal ECG, exertional, supine, palpitations, structural heart disease, family SCD hx) → "Echocardiography + Continuous cardiac monitoring (telemetry if inpatient, ILR if outpatient) + Consider EP study if structural heart disease with unexplained syncope." Branch 3 (right, orange): "Unexplained After Initial Evaluation" → "Risk stratify (high vs low risk)." High risk: "Inpatient monitoring, echo, further testing." Low risk (young, vasovagal features): "Prolonged cardiac monitoring (Holter → event recorder → ILR if recurrent); Tilt table testing if vasovagal suspected but atypical." Bottom box: "Special situations: Exertional syncope → Exclude AS, HCM, coronary anomaly, arrhythmia (stress test + echo mandatory). Syncope + family history SCD → Screen for channelopathies (Brugada, LQTS, CPVT), HCM, ARVC." Use green for benign diagnoses, red for high-risk cardiac, yellow for intermediate.
</image>

## Vasovagal Syncope

### Pathophysiology

The traditional pathophysiologic model of vasovagal syncope involves the Bezold-Jarisch reflex, whereby vigorous contraction of an under-filled ventricle activates ventricular mechanoreceptors, triggering paradoxical vagal activation with concurrent sympathetic withdrawal. This produces the dual hemodynamic response of bradycardia and vasodilation, resulting in hypotension, cerebral hypoperfusion, and syncope. Contemporary understanding recognizes a more complex model involving central autonomic processing in the brainstem, cortical override of the baroreflex arc, and serotonergic pathways. The hemodynamic response has two components: a cardioinhibitory component where bradycardia or asystole predominates, and a vasodepressor component where hypotension occurs without significant bradycardia. The mixed type, combining elements of both, is the most common presentation.

### Tilt Table Testing

Head-up tilt table testing is performed at a 70-degree angle for 20 to 45 minutes during the passive phase, followed by provocation with sublingual nitroglycerin at 0.4 mg or intravenous isoproterenol infusion if the passive phase is negative. A positive test requires reproduction of syncope or presyncope with documented hypotension and/or bradycardia. The response is classified as Type 1 (mixed) when heart rate decreases but not below 40 beats per minute for less than 10 seconds, Type 2A (cardioinhibitory without asystole) when heart rate falls below 40 for more than 10 seconds without asystole exceeding 3 seconds, Type 2B (cardioinhibitory with asystole) when asystole exceeds 3 seconds, and Type 3 (vasodepressor) when blood pressure drops without significant heart rate decrease. The test has a sensitivity of approximately 60 to 70% and specificity of 85 to 90%, with false positives possible. Clinical utility remains debated, and tilt testing is most useful when the history is atypical and the diagnosis is uncertain.

### Pharmacologic Options for Vasovagal Syncope

| Agent | Dose | Mechanism | Key Trial Evidence | Notes |
|---|---|---|---|---|
| Midodrine | 5-15 mg TID | Alpha-1 agonist (vasoconstriction) | POST-3: no benefit in unselected patients | Avoid supine hypertension; last dose by 4 PM |
| Fludrocortisone | 0.1-0.2 mg daily | Mineralocorticoid (volume expansion) | POST-2: modest benefit in younger patients with low BP | Monitor K+, BP |
| Metoprolol | Standard dose | Beta-blocker | POST-1: NO benefit | NOT recommended; possible exception age >42 (POST-5) |
| SSRIs (paroxetine, sertraline) | Standard dose | Central serotonin modulation | Limited evidence | Consider for refractory cases |
| Pacemaker (CLS) | -- | Closed-loop stimulation | BIOSync CLS: 77% recurrence reduction | ONLY for cardioinhibitory type with asystole >3 sec |

### Management

The foundation of vasovagal syncope management is education and reassurance about the benign nature of the condition, combined with identification of triggers and lifestyle modifications including adequate hydration at 2 to 3 liters daily and salt intake up to 10 grams daily when not contraindicated. Physical counterpressure maneuvers, including leg crossing with muscle tensing, hand gripping, and arm tensing, can be applied during the prodromal phase to abort an impending episode, and patients should be trained in these techniques. Tilt training involves progressive exposure to upright posture through 20 to 40 minutes of standing against a wall daily, though evidence supporting its efficacy is limited.

Pharmacologic therapy offers limited efficacy. Midodrine, an alpha-1 agonist at 5 to 15 mg three times daily, provides modest benefit but must be avoided in the setting of supine hypertension, and the POST-3 trial showed no benefit in unselected vasovagal syncope patients. Fludrocortisone at 0.1 to 0.2 mg daily provides volume expansion, with the POST-2 trial showing modest benefit primarily in younger patients with low baseline blood pressure, with monitoring for hypokalemia and hypertension. Beta-blockers are not recommended, as the POST-1 trial with metoprolol demonstrated no benefit, and they may worsen the vasodepressor component. A possible exception exists for patients over 42 years of age based on the POST-5 subanalysis. Selective serotonin reuptake inhibitors such as paroxetine and sertraline have limited evidence but are theoretically justified through modulation of central serotonergic pathways, and may be considered for refractory cases.

Pacemaker implantation should be considered only for cardioinhibitory vasovagal syncope with documented prolonged asystole exceeding 3 seconds with symptoms or exceeding 6 seconds without symptoms. The BIOSync CLS trial demonstrated that closed-loop stimulation pacemaker technology reduced syncope recurrence by 77% in patients over 40 years with cardioinhibitory vasovagal syncope and asystole exceeding 3 seconds. Standard dual-chamber pacing has been less effective, with the VPS-II and SYNPACE trials yielding negative results.

## Orthostatic Hypotension

### Definitions

Classical orthostatic hypotension is defined as a sustained systolic blood pressure drop of 20 mmHg or greater or diastolic blood pressure drop of 10 mmHg or greater within 3 minutes of standing. Initial orthostatic hypotension is a transient systolic blood pressure drop exceeding 40 mmHg within 15 seconds of standing that recovers within 30 to 60 seconds, causing transient lightheadedness upon standing. Delayed orthostatic hypotension occurs after 3 minutes of standing and may progress to classical orthostatic hypotension over time, often representing early autonomic failure.

The distinction between neurogenic and non-neurogenic orthostatic hypotension is clinically important. Neurogenic orthostatic hypotension is characterized by inadequate compensatory heart rate increase, defined as less than 15 beats per minute rise or a heart rate-to-systolic blood pressure ratio below 0.5. Non-neurogenic causes demonstrate an appropriate tachycardic response and include dehydration, hemorrhage, and medication effects.

### Causes of Neurogenic OH

Neurodegenerative conditions represent major causes of neurogenic orthostatic hypotension, including Parkinson disease with a prevalence of 50 to 60%, multiple system atrophy also known as Shy-Drager syndrome, pure autonomic failure, and dementia with Lewy bodies. Peripheral neuropathies are another important category, with diabetes being the most common secondary cause, followed by amyloidosis of both transthyretin and light chain types, autoimmune conditions including Guillain-Barre syndrome and autoimmune autonomic ganglionopathy, and paraneoplastic syndromes. Iatrogenic causes include spinal cord injury, post-sympathectomy states, and post-organ transplantation. Drug-induced orthostatic hypotension is the most common cause overall, resulting from alpha-blockers, diuretics, nitrates, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, tricyclic antidepressants, antipsychotics, and antiparkinsonian agents.

### Management

Non-pharmacologic measures form the cornerstone of orthostatic hypotension management. Bolus water drinking of 500 mL rapidly before standing produces a pressor effect within 5 to 15 minutes. Dietary salt intake should be increased. Compression garments, with waist-high garments preferred over below-knee stockings for superior efficacy, provide additional benefit. Head-of-bed elevation at 10 to 15 degrees reduces nocturnal diuresis and improves morning blood pressures. Patients should avoid prolonged recumbency, hot environments, and large meals that may exacerbate postprandial hypotension. Small, frequent meals are recommended.

Pharmacologic therapy includes midodrine at 2.5 to 10 mg three times daily, with the last dose administered before 6 PM to avoid supine hypertension. This alpha-1 agonist is the most evidence-based pharmacotherapy for orthostatic hypotension. Fludrocortisone at 0.1 to 0.3 mg daily provides volume expansion through its mineralocorticoid effect, with monitoring of electrolytes, weight, and supine blood pressure. Droxidopa (Northera), a norepinephrine prodrug at 100 to 600 mg three times daily, is FDA-approved for neurogenic orthostatic hypotension and improves standing systolic blood pressure, though the duration of effect may diminish over time. Pyridostigmine at 30 to 60 mg three times daily enhances sympathetic ganglionic transmission as an acetylcholinesterase inhibitor, with the advantage of not worsening supine hypertension, though its effect is modest. Atomoxetine, a norepinephrine reuptake inhibitor at 10 to 18 mg twice daily, has emerging evidence supporting its use in neurogenic orthostatic hypotension.

Supine hypertension coexists in 50 to 70% of patients with neurogenic orthostatic hypotension and requires careful management. Strategies include avoiding midodrine in the supine position, administering short-acting antihypertensives at bedtime such as losartan 25 to 50 mg or a nitroglycerin patch at 0.1 to 0.2 mg/hour removed in the morning, and maintaining head-of-bed elevation.

## Postural Orthostatic Tachycardia Syndrome (POTS)

### Definition and Diagnosis

Postural orthostatic tachycardia syndrome is defined by a sustained heart rate increase of 30 beats per minute or greater, or an absolute heart rate of 120 beats per minute or greater, within 10 minutes of standing, occurring without orthostatic hypotension, in the context of chronic symptoms persisting for 3 to 6 months or longer. For adolescents, a heart rate increase criterion of 40 beats per minute or greater is applied. The condition predominantly affects females with a 5:1 sex ratio, typically manifesting between ages 15 and 50. The estimated prevalence is 170 per 100,000, with significantly increased recognition following the COVID-19 pandemic.

### POTS Subtypes

| Subtype | Mechanism | Key Features | Standing Norepinephrine | Preferred Treatment |
|---|---|---|---|---|
| Neuropathic | Partial autonomic neuropathy (lower extremity vasoconstriction failure) | Dependent blood pooling; sudomotor dysfunction | Normal to mildly elevated | Midodrine, compression garments, exercise |
| Hyperadrenergic | Excessive sympathetic activation | Tremor, anxiety, palpitations; BP may rise with standing | >600 pg/mL | Central sympatholytics (clonidine, methyldopa); low-dose propranolol |
| Hypovolemic | Reduced plasma volume (~600 mL below normal) | Inadequate renin-aldosterone activation | Variable | Fludrocortisone, salt/fluid loading; AVOID beta-blockers |
| Autoimmune | Autoantibodies (ganglionic AChR, adrenergic receptor) | Often post-viral; overlaps with MCAS and EDS | Variable | IVIG (case reports); treat associated conditions |

### Subtypes

Several pathophysiologic subtypes of postural orthostatic tachycardia syndrome have been identified, though considerable overlap exists among them. Neuropathic POTS involves partial autonomic neuropathy affecting lower extremity vasoconstriction, producing dependent blood pooling in the legs and demonstrable sudomotor dysfunction on autonomic testing. Hyperadrenergic POTS features excessive sympathetic activation with standing norepinephrine levels exceeding 600 pg/mL, blood pressure that may increase with standing, and prominent tremor, anxiety, and palpitations. Hypovolemic POTS is characterized by reduced plasma volume, approximately 600 mL below normal, with inadequate renin-aldosterone activation. Autoimmune POTS is associated with autoantibodies including ganglionic acetylcholine receptor and adrenergic receptor antibodies, may follow viral illness, and overlaps with mast cell activation syndrome and hypermobility syndromes such as Ehlers-Danlos syndrome.

### Management

Non-pharmacologic interventions are the cornerstone of POTS management. Fluid intake should reach 2 to 3 liters daily, with salt intake of 10 to 12 grams daily supplemented by salt tablets. Waist-high compression garments reduce venous pooling. A structured exercise reconditioning program is the most effective long-term treatment, beginning with recumbent exercises such as rowing, swimming, and recumbent cycling, and gradually progressing to upright exercise over 3 to 6 months following the Levine or CHOP protocol. Prolonged standing and heat exposure should be avoided.

Pharmacologic options are selected based on the predominant subtype. Fludrocortisone at 0.1 to 0.2 mg daily provides volume expansion. Midodrine at 5 to 10 mg three times daily improves vasoconstriction. Low-dose beta-blockers, including propranolol at 10 to 20 mg three times daily or 60 to 80 mg long-acting daily, reduce the tachycardic response but should be avoided in hypovolemic POTS where they may worsen symptoms. Bisoprolol at 2.5 to 5 mg has been studied in the POTS-BOSS trial. Ivabradine at 5 to 7.5 mg twice daily, used off-label, provides selective heart rate reduction without blood pressure effects and is increasingly utilized. Pyridostigmine at 30 to 60 mg three times daily enhances ganglionic neurotransmission. For hyperadrenergic POTS, central sympatholytic agents such as methyldopa or clonidine may be helpful. Intravenous saline infusion provides acute relief for severe flares, though chronic home infusions remain controversial due to the risks associated with central venous access.

<image>
A physiologic comparison diagram showing normal autonomic response to standing versus three pathologic states. Four panels showing a human figure in supine and standing positions with hemodynamic parameters. Panel 1 (Normal): Supine BP 120/80, HR 70. Standing: brief BP dip, baroreflex activation, appropriate vasoconstriction (depicted as narrowed leg vessels), HR rises to 85, BP recovers to 118/78. Labels: intact baroreflex, sympathetic vasoconstriction, adequate plasma volume. Panel 2 (Vasovagal Syncope): Standing: initial compensation, then paradoxical vagal activation (vagus nerve highlighted), HR drops to 40 (bradycardia), BP crashes to 60/30 (vasodilation shown as dilated vessels), collapse with LOC, recovery supine. Panel 3 (Neurogenic OH): Standing: inadequate vasoconstriction (dilated leg vessels highlighted, damaged sympathetic nerves shown as interrupted lines), BP drops to 80/50 within 3 minutes, HR rises minimally to 78 (blunted chronotropic response, HR/SBP ratio <0.5), presyncope/syncope. Panel 4 (POTS): Standing: excessive blood pooling in legs (blue-colored dilated veins), BP maintained but HR surges from 72 to 115 within 10 minutes (>30 bpm rise), no syncope but significant symptoms (lightheadedness, palpitations, tremor listed). Each panel labeled with the condition name, key hemodynamic values, and pathophysiologic mechanism.
</image>

## Cardiac Monitoring for Unexplained Syncope

### Cardiac Monitoring Options for Unexplained Syncope

| Device | Duration | Diagnostic Yield | Best Suited For | Key Limitation |
|---|---|---|---|---|
| Holter monitor | 24-48 hours | 1-2% | Daily or near-daily events | Very low yield for infrequent syncope |
| External event recorder/patch (Zio, BioTel) | 2-4 weeks | Higher than Holter | Weekly to monthly events | Patient compliance; skin irritation |
| Implantable loop recorder (Reveal LINQ, Biomonitor) | 3-4 years | 40-60% (ISSUE-3, PICTURE, EaSy-AS) | Infrequent events (>monthly intervals); recurrent unexplained syncope | Invasive (minor procedure); cost |
| Electrophysiology study | Single session | 10-15% (if normal ECG/echo) | Structural heart disease with suspected arrhythmia; bifascicular block (HV interval); preexcitation | Low yield without structural disease |

### Holter Monitor

The 24 to 48-hour continuous Holter monitor recording is useful when syncope occurs on a daily or near-daily basis. However, the diagnostic yield for identifying the cause of syncope is only 1 to 2%, limiting its clinical utility for infrequent episodes.

### External Event Recorder/Patch Monitor

External event recorders and patch monitors provide 2 to 4 weeks of continuous recording using devices such as the Zio patch or BioTel monitors, with patients able to mark symptomatic events. These devices offer a higher diagnostic yield than Holter monitors and are increasingly used as the first-line ambulatory monitoring strategy. They are best suited for syncope occurring on a weekly to monthly basis.

### Implantable Loop Recorder (ILR)

The implantable loop recorder, a subcutaneous device such as the Reveal LINQ or Biomonitor, provides continuous monitoring for up to 3 to 4 years. The ISSUE-3 and PICTURE studies demonstrated that the implantable loop recorder achieves the highest diagnostic yield in recurrent unexplained syncope, identifying a diagnosis in approximately 40 to 60% of patients over the monitoring period, with findings guiding therapy decisions including pacemaker implantation, antiarrhythmic therapy, or confirmation that no therapy is needed. Implantable loop recorder placement is recommended when the initial evaluation is non-diagnostic, syncope is recurrent, high-risk features suggest an arrhythmic cause, and episodes are infrequent at more than monthly intervals. The EaSy-AS trial demonstrated that early implantable loop recorder implantation in unexplained syncope presenting to the emergency department improved diagnostic yield, supporting a strategy of early implantation rather than exhaustive sequential testing.

### Electrophysiology Study

Electrophysiology study has a low diagnostic yield for unexplained syncope when the electrocardiogram and echocardiogram are normal, at approximately 10 to 15%. It is indicated when structural heart disease is present with suspected arrhythmic syncope, in patients with bifascicular block where assessment of the HV interval is needed with an HV interval exceeding 70 milliseconds or infranodal block during atrial pacing suggesting the need for permanent pacing, in suspected sinus node dysfunction, and in patients with ventricular preexcitation. Bundle of His recording demonstrating an HV interval exceeding 70 milliseconds or infranodal block during atrial pacing constitutes an indication for pacemaker implantation.

## Key Clinical Pearls

- History is the most powerful diagnostic tool in syncope -- a carefully obtained account from the patient AND witnesses correctly identifies the cause in up to 50% of cases without any testing
- Syncope during exertion is a RED FLAG that mandates cardiac evaluation (echo, stress test, arrhythmia monitoring) before attributing it to vasovagal mechanism -- it may indicate HCM, AS, coronary anomaly, or catecholaminergic VT
- The ILR is the highest-yield diagnostic tool for unexplained recurrent syncope -- it should be implanted early (after initial non-diagnostic evaluation) rather than after exhaustive testing; EaSy-AS supports this approach
- Pacemaker for vasovagal syncope should ONLY be considered with documented cardioinhibitory mechanism (asystole > 3 seconds) -- the BIOSync CLS trial showed benefit with closed-loop stimulation, but standard DDD pacing has NOT been shown to be consistently beneficial
- POTS is a real physiologic disorder, not a psychosomatic condition -- structured graduated exercise reconditioning (starting with recumbent exercise) is the most effective long-term treatment and should be prescribed for ALL POTS patients
- Orthostatic vitals should be measured correctly: patient supine for >= 5 minutes first, then BP immediately after standing and at 3 minutes -- a single random standing BP is insufficient to diagnose or exclude orthostatic hypotension

## References

- Brignole M, et al. 2018 ESC Guidelines for the Diagnosis and Management of Syncope. Eur Heart J. 2018;39:1883-1948.
- Sheldon RS, et al. 2022 Canadian Cardiovascular Society/Canadian Autonomic Research Society Comprehensive Clinical Guideline on the Evaluation and Management of Autonomic Dysfunction. Can J Cardiol. 2022;38:S27-S69.
- Brignole M, et al. Closed-Loop Stimulation for Vasovagal Syncope (BIOSync CLS). NEJM. 2021;384:1042-1052.
- Sheldon RS, et al. Prevention of Syncope Trial (POST-2). JACC. 2016;68:1-9.
- Raj SR, et al. Canadian Cardiovascular Society Position Statement on Postural Orthostatic Tachycardia Syndrome and Related Disorders. Can J Cardiol. 2020;36:357-372.