Syncope is a common clinical syndrome defined by sudden transient total loss of consciousness and postural tone resulting in a fall caused by global cerebral hypoperfusion. The subsequent recovery is spontaneous, complete, and relatively prompt; without neurologic sequelae. It manifests as a symptom complex characterized by light-headedness, generalized muscle weakness, giddiness, visual blurring, tinnitus, and gastrointestinal (GI) symptoms.
Pre-syncope refers to a situation in which there is reduction of cerebral blood flow and a sensation of impending loss of consciousness, although the patient does not actually looses consciousness.
Syncope occurs secondary to acute transient decrease in cerebral perfusion due to a variety of mechanisms.
Cerebral perfusion is largely dependent on systemic arterial pressure which in turn is dependent on cardiac output (CO) and peripheral vascular resistance (PVR). Anything that lowers either CO or PVR or both affects the systemic arterial pressure and cerebral perfusion and thereby predisposes a person to syncope. In addition to these 2 factors, any impairment to blood flow in the cerebrovascular vessels themselves, such as vasoconstriction, also increases the chances of syncope.
The degree of venous return is important because the heart cannot pump out blood that it does not receive. Obviously, diminished effective blood volume predisposes to syncope, especially in conjunction with postural change. Cardiac output may also be impaired when the heart itself performs inadequately owing to bradyarrhythmias, tachyarrhythmias, myocardial dysfunction, or valvular heart disease.
During states of low venous return, as during orthostatic stress, cardiac output is limited by the rate of venous filling rather than by the frequency with which the heart empties. With high heart rates, the time available to adequately fill the ventricle is shortened; thereby, the stroke volume is diminished due to a combination of decreased venous return and filling time.
The relationship between heart rate (HR) and cardiac output (CO) is well-known: CO = SV x HR.
In order for a person to lose consciousness, the reduction of blood flow must affect the reticular activating system of the brain stem, thalamus, or both cerebral hemispheres simultaneously.
Normally, with the assumption of an upright posture, there is a transient reduction in blood pressure that results in a decrease in baroreceptor afferent input to the NTS. This is referred to as the unloading of the baroreceptors. The premotor neurons in RVLM are disinhibited and exert their sympathetic noradrenergic input to increase the peripheral vascular resistance in the blood vessels of skeletal muscles and the mesenteric blood vessels by causing them to vasoconstrict. This then prevents venous pooling in the abdomen and lower limbs (600 - 800 mL of blood) and is the primary mechanism to prevent orthostatic hypotension. Similarly, the decrease in baroreceptor afferent input to the NTS and in turn to nucleus ambiguus inhibits the cardiovagal output resulting in an increase in HR. So there is tachycardia and increased PVR leading to a rise in BP.
The integrity of a number of control mechanisms is crucial for maintaining adequate perfusion of the brain and cerebral oxygen delivery after sudden changes in blood pressure. Arterial baroreceptor-induced adjustments of sympathetic vasomotor tone affecting PVR, cardiac contractility, and heart rate act almost instantaneously to maintain sufficient arterial BP and cerebral perfusion after provocations such as orthostatic stress.
Vasomotor outflow is the most important arterial baroreceptor adjustment. The central modulation of vasomotor outflow is reinforced by local control in dependent areas, such as the venoarteriolar axon reflex and the myogenic response, and by activation of the humoral system (RAA and vasopressin constriction).
Central blood volume - preload is of paramount importance for the beat-to-beat adjustment of arterial pressure. Intravascular volume regulation, incorporating the renal-body fluid (aldosterone, antidiuretic hormone) control system and oral fluid intake, helps to maintain cerebral blood volume.
Cerebrovascular autoregulation permits cerebral blood flow to be maintained over a relatively wide range of sudden changes in perfusion pressures.
Transient failure of these control mechanisms, or effects from other factors such as vasodilator drugs, diuretics, hemorrhages, or dehydration, any of which reduces systemic blood pressure below the autoregulation of the cerebrovascular tone, may induce a syncopal episode. Risk of failure of normal protective compensatory mechanisms is greatest older or ill patients. The experience from tilt-table testing has taught us that a decrease in systolic blood pressures to 60 mm Hg or less invariably leads to syncope.
presyncopal, syncopal, and recovery phases.
Presyncopal phase: Patient is awake and able to related to an accurate history. Pt. is usually standing, experiences a sensation of light-headedness, dizziness, weakness, yawning, a feeling of warmth, nausea, vomiting, and profuse sweating. Patient may have transient blindness.
Syncopal phase: LOC, loss of postural tone, resulting in fall to the ground from muscle weakness. If syncope truly occurred, the patient will not have any memory of the events of this phase and will not provide an accurate history. Collateral information from witnesses regarding onset of syncope, duration of LOC, seizure activity, circumstances around the fall, likely trauma. A complete lack of muscle tone or myoclonic jerks is common in syncope, unlike seizure activity where tonic-clonic activity and post-ictal confusion is seen. LOC is brief, followed by immediate recovery.
Recovery phase: Ask regarding rate of recovery from patient or/and witnesses. Confusion or delayed recovery to normal suggests post-ictal state, hypoglycemia, or CNS lesion. Patient with syncope usually regains normal mental function rapidly, with near normal mentation. Check VS, BS, ECG to provide some insight into the cause of syncope.
HTN, CAD, DM, VTE, CVA. Meds (anti-HTN, QT-prolonging agents, proarrhythmics, psychotropic, vasodilators) may lead to syncope secondary to dysrhythmia and hypotension.
Impaired cerebral perfusion: syncope, fainting
Cerebral ischemia
Migraine
Epileptic seizures
Metabolic disturbances
Sudden increased ICP
Sleep disorders
Cardiac:
Arrhythmias:
AV block
SA block
Paroxysmal tachycardia
SVT: AF with RVR, AF, WPW syndrome.
VF, VT
Long QT syndrome
Short QT syndrome
Brugada syndrome
Reflex cardiac arrhythmias
Carotid sinus hypersensitivity
Glossopharyngeal neuralgia
Decreased cardiac output:
Outflow obstruction
Inflow obstruction
Cardiomyopathy
Increase intrathoracic pressure
Cough, straining (playing trumpet, defecation, valsalva maneuver)
Hypovolemia
Loss of blood
Diarrhea, vomiting, salt-losing kidney, adrenal insufficiency
Pheochromocytoma
Hypotension:
Vasovagal attack
Drugs
Dysautonomia
Cerebrovascular:
TIA
Carotid disease (anterior circulation)
Vertebrobasilar disease (posterior circulation)
Cerebral vasospasm (migraine)
SAH
HTN encephalopathy
Takayasu disease
Pulmonary embolism
Metabolic:
Hypoglycemia
Anemia
Hypoxia
Drugs
Hyperventilation
Structural abnormalities in the autonomic nervous system (efferent sympathetic pathways)
Primary: PAF, MSA, PD
Secondary: DM, uremia, spinal cord lesions,
Medications: Vincristine
Vasovagal
Sinus caroticus syndrome, glossopharyngeal neuralgia
Situational (swallowing, micturition, defecation)
Recurrent, unexplained syncope, particularly in an individual with structural heart disease, and is associated with a high risk of death (40% mortality in 2 years).
Epidemiology:
Vasovagal syncope: 21.2%
Cardiac syncope: 9.5%
Orthostatic hypotension: 9.4%
Medication effects: 6.8%
Seizure: 4.9%
Stroke: 4.1%
Unknown: 36.6%
Lifetime prevalence of syncope in general population for people >60 years: 20% to 40%.
Bimodal distribution in age: 15 - 20 years and 80 years.
The frequency of myoclonic or tonic activity during syncope is high (approximately 70%–90%). Myoclonus associated with syncope tends to be asynchronous, multifocal rather than generalized, and brief (less than 30 seconds). Tonic movements are less frequent and less pronounced in syncope, and more common after profound cerebral hypoxia (e.g., prolonged asystole, breath-holding spells). Even after a prolonged syncope lasting 1 to 2 minutes, the postictal confusion rarely lasts more than 30 seconds. Thus, longer-lasting disorientation suggests an epileptic seizure, although an exception would be frontal lobe seizures, which can be associated with very brief postictal periods. EEG during syncope shows a sequence of changes: diffuse high-amplitude slowing at the onset of unconsciousness; suppression; reappearance of slow activity; and return of normal background activity. This sequence represents the final common path for global cerebral hypoxia, and is independent of the mechanism of syncope and of the clinical presentation as convulsive or nonconvulsive syncope.
A prodrome of presyncope marked by dizziness pallor is the rule. Bradycardia may be seen shortly after the episode, and recovery is usually rapid. If the clinical picture is not clear, the tilt table study is done to provoke vasovagal syncope in order to establish the diagnosis with the sensitivity and specificity of approximately 80%. Sudden head up tilting in patient with vasovagal syncope produces an increase in myocardial contractility, which in turn leads to excessive stimulation of left ventricle and mechanical receptors (C fibers) and an exaggerated reflex vagal response. No specific intervention is required and the prognosis is excellent. Up to 80% the patient with recurrent vasovagal syncope and positive tilt test respond to treatment with a beta blocker such as atenolol 25-100 mg PO q.d. This blunts the cardiac inotropic response to a fall in BP and prevents the overly sensitive reflex vagal response. Approximately half of patients who do not respond to a beta blocker or other agents will respond to paroxetine 20 mg p.o. daily, a selective SSRI.
Is unusual disorder seen exclusively in older individuals and results from hypersensitivity or baroreceptors in the carotid sinus. External pressure of the neck (like turning the head while wearing a tight collar, results in an exaggerated vagal response and fall in BP. Carotid massage can be used with ECG monitoring to establish the diagnosis, but this should be performed with caution since patient may end up getting a stroke.
Transient ischemic attack. The vertebrobasilar stenosis or occlusion is a rare cause of syncope. The diagnosis as suggested by symptoms or signs of focal brainstem ischemia (diplopia, vertigo, ataxia, nystagmus, dysarthria, dysphagia, facial numbness, unilateral or bilateral weakness, or sensory loss) either before or after the event. Deficits referable to posterior cerebral artery, particularly hemianopia may also occur. Syncope following prolonged head extension ("beauty pallor syncope") in patients with atherosclerotic vertebrobasilar disease has been described. Transcranial and duplex Doppler ultrasonography, CT or MRA, or conventional angiography is used to establish the diagnosis.
Subclavian steal. is an unusual cause of vertebrobasilar insufficiency. It results from occlusion of one of the subclavian arteries proximal to the origin of the vertebral artery. The distal subclavian artery is hence supplied by retrograde flow from the ipsilateral vertebral artery, which steal flow from the basilar and contralateral vertebral arteries, resulting in intermittent hemodynamic flow failure in the posterior circulation.
Unilateral carotid stenosis or occlusion does not cause syncope. However, in very rare instances, syncope may result from severe bilateral disease, particularly with superimposed reduction of blood pressure.
Primary autonomic failure: Shy-Drager or Riley-Day syndrome; MSA.
Autonomic ganglionopathy: Autoimmune (antecedent viral illness) or paraneoplastic (SCLC). Sx develop over weeks. Dysfunction in autonomic system. Antibody to ganglionic nictoninic ACh-rcp in serum.
Pure autonomic failure (Bradbury-Eggleston syndrome): Attributed to loss of intermediolateral cell column neurons. Alpha-synucleinopathy with Lewy bodies seen. In men earliest sx is impotence. No an acute condition.
Neuropathies: DM, amyloidosis, BGS, AIDS, alcoholic neuropathy, hepatic prophyria, beriberi, and autoimmune subacute autonomic neuropathy and small fiber neuropathies.
It is a heterogenous condition with orthostatic intolerance due to dysautonomia and is characterized by rise in heart rate above 30 bpm from base line or to more than 120 bpm within 5-10 min of standing with or without change in blood pressure which returns to base line on resuming supine position.
This condition present with various disabling symptoms such as light headedness, near syncope, fatigue, nausea, vomiting, tremor, palpitations and mental clouding, etc . However there are no identifiable signs on clinical examination and patients are often diagnosed to have anxiety disorder. The condition predominantly affects young women between the ages of 15-50 years but is rarely described in older people.
Pathophysiology: The various pathophysiological mechanisms involved in POTS are:
High level of standing norepinephrine level (due to reduced norepinephrine transporter expression resulting increased systemic norepinephrine spill over)
Presence of ganglionic acetylcholine receptor antibodies;
Alpha 1 adrenergic receptor denervation or hyposensitivity
Beta adrenergic super sensitivity
Peripheral autonomic denervation with preserved cardiac and cerebral innervations
Partial renal sympathetic denervation leading to reduced renin/Aldosterone.
Increased angiotensin II level with blunted responsiveness of receptors to angiotensin II
Low blood volume and Red cell volume;
Abnormal vascular structure with impaired venous capacitance
Increased capillary permeability.
Not all of these mechanisms present in any one patient and treatment should be tailored accordingly. Symptoms are most likely due to cerebral hypoperfusion.
Types of POTS:
Primary
Secondary
The primary form is not associated with or caused by other chronic disorders. Here the onset is usually abrupt particularly when it occurs following viral illness, immunisation, pregnancy or surgery. An exception is the developmental form which occurs following a period of rapid growth. In this case it runs a slow progress to reach a peak within 2 years. Two major types of primary forms are identified. They are partial dysautonomic and hyperadrenergic forms:
Partial dysautonomic form is the most frequent form and is due to peripheral autonomic neuropathy which results in excessive pooling of blood in blood vessels of lower limbs and mesenteric circulation with the reflex tachycardia. There is inability of peripheral blood vessels to constrict. Onset is abrupt. It is usually autoimmune mediated. Antibodies to ganglionic acetylcholine receptors are often found in patients with post viral autonomic neuropathy.
Hyperadreneric form is less frequent. Tachycardia occurs due to elevated catecholamine release. Onset is usually gradual. It is usually a familial condition where there is rise in norepinephrine level on standing which causes the orthostatic tachycardia and orthostatic intolerance. The rise in norepinephrine is due to reduced clearance secondary to poorly functioning reuptake transporter protein. Standing catecholamine level is elevated. These patients suffer from profuse sweating, anxiety, tremulousness, tachycardia and hypertension.
Secondary POTS can occur in conditions that affect the peripheral autonomic nervous system such as diabetes mellitus, amyloidosis, sarcoidosis, and paraneoplastic syndromes, or following chemotherapy.
Management of POTS is multifaceted and includes discontinuation of any medications that could contribute to orthostatic intolerance, such as α-adrenoceptor antagonists, diuretics, cGMP-specific phosphodiesterase type 5 inhibitors (sildenafil), and organic nitrates and nitrites, along with identifying those conditions that may cause secondary POTS.
Treating POTS patients comprises non-pharmacological and pharmacological interventions. Conservative measures for patients with mild POTS symptoms include plasma volume expansion and increasing dietary salt and fluid intake. Pharmacotherapy is needed for patients with moderate to severe POTS, and, currently, no drug has been officially approved by the US Food and Drug Administration (FDA) for treating POTS. In fact, most drugs that are given to POTS patients are usually prescribed “off label” and include fludrocortisone, desmopressin, and, sometimes, erythropoietin. Other drugs which can also be therapeutically beneficial in patients with POTS are (1) drugs that increase peripheral vascular resistance such as midodrine, a prodrug whose active metabolite is an α-adrenoceptor antagonist, and somatostatin analogs; (2) drugs that can modify the central and peripheral activity of the sympathetic nervous system such as β-adrenoceptor antagonists (mainly propranolol), serotonin and norepinephrine uptake inhibitors, and combined α- and β-adrenoceptor antagonists; and (3) drugs that reduce the sympathetic tone such as clonidine.
Investigations: Head up tilt (HUT) is the investigation of choice although some studies suggest that standing haemodynamics is more specific. It is important to rule out other conditions which cause tachycardia such as phaeochromocytoma, carcinoid, thyrotoxicosis, cardiac arrhythmia, etc. Tachycardia in these conditions is not related to change in posture. Important investigations are blood tests which should include full blood count, renal function, thyroid function, calcium level, glucose, catecholamines on standing from supine position. Twenty-four hours urine collection for 5HIAA, catecholamines, sodium level are relevant investigations in POTS to rule out other causes of tachycardia and aim treatment options. Routinely an ECG should be performed and further investigations such as 24 h monitoring and echocardiogram are carried out if indicated.
Management: Review of medications which can aggravate POTS and appropriately stopping these medications; these include: drugs that enhance vasodilatation-alpha adrenoreceptor blockers, angiotensin converting enzyme inhibitor (ACEI), calcium channel blockers and nitrates; drugs that enhance tachycardia-beta adrenoreceptor stimulants, tricyclic antidepressants; and drugs that worsens volume depletion-diuretics and ACEI.
Treatment of POTS is challenging due to the potential for adverse effects from the above mentioned drugs and the limited effectiveness of non-pharmacologic treatments. Many POTS patients have difficulty achieving adequate control of their symptoms. In addition, none of the abovementioned medications are tailored specifically to blunt the increase in HR that underlies the many symptoms of POTS.
Vasoconstrictors: Fludrocortisone is the most commonly used drug in orthostatic intolerance. Its action is mediated by improving peripheral sensitivity of alpha adrenoceptors, fluid and salt retention. Midodrine is an alpha-1 adrenoreceptor agonist not only increases the peripheral vascular resistance but also helps orthostatic intolerance by having an effect on heart rate. Other vasoconstrictors used with variable results are: methylphenidate - increases vasoconstriction by increasing catecholamine release and inhibiting monoamine oxidase; erythropoietin: increases the sensitivity of angiotensin II; clonidine is a central sympatholytic and increases peripheral vascular resistance; and octreotide: somatostatin analogue is potent vasoconstrictor.
Heart rate limiting drugs: Beta blockers are the main group of drugs and among them propranolol is favored by clinicians. There are limited studies with regards to the dosage at which it is effective in treating POTS. Moderate dose of propranolol (20 mg) not only reduces heart rate but also improves symptoms, whereas higher dose (80 mg) is effective in reducing heart rate but does not improve symptoms. In fact it has been reported to worsen symptoms. Other drugs which can reduce heart rate and alleviate symptoms are selective serotonin reuptake inhibitors (SSRI) and selective noradrenalin reuptake inhibitors. SSRI have been used for cardiogenic syncope and orthostatic hypotension. Serotonin plays and important role in central control of heart rate.
There is some anecdotal evidence that some POTS patients can be successfully treated with ivabradine, an anti-anginal agent designed to slow the HR. Ivabradine is a selective antagonist of the If channel, an ionic current that determines the slope of diastolic depolarization (phase IV action potential). Accordingly, ivabradine controls the time interval between successive action potentials and the HR. Ivabradine also reduces the firing rate of pacemaker cells in the sinoatrial (SA) node, where it mainly influences the intrinsic HR at concentrations that do not affect other cardiac currents, and has no negative inotropic or lusitropic effects. In view of its ability to slow the HR without affecting other cardiovascular functions, we posited that ivabradine may be an ideal medication for treating POTS patients. We report herein on the results of an investigation in which the effect of ivabradine on the hemodynamics and sympathovagal balance of POTS patients was studied.
Ivabradine (Corlanor) is a selective If channel blocker (hyperpolarization-activated cyclic nucleotide-gated or HCN channel in SA node) that reduces heart rate by selectively inhibiting cardiac pacemaker current without affecting other cardiovascular functions. In case reports and case series, it was shown to improve symptoms in patients with postural tachycardia syndrome (POTS).
Ivabradine was originally developed for the treatment of chronic stable angina pectoris. Ivabradine blocks the If channel (funny channel, HCN2/4 channel), which is a mixed Na+–K+ inward current that causes hyperpolarization of the membrane and is highly expressed in the SA node and atrioventricular node. This channel is typically controlled by the sympathetic nervous system. The sympathetic and parasympathetic nervous systems cause an increase and a decrease, respectively, in the Na+ inward current and results in either tachycardia or bradycardia. Currently, ivabradine is approved for use in Europe only for anginal syndromes and inappropriate sinus tachycardia syndrome. The activity of this channel is regulated by the autonomic nervous system (ANS). The sympathetic arm of the ANS activates the β1-adrenoreceptor; its second messenger, cyclic AMP, increases If channel conductance. This increased conductance permits more Na+ ions to move into the cells of the SA node. The HR increases due to the reduced polarity (phase IV of the action potential) of these cells. Parasympathetic or vagal tone of the heart is facilitated by M2 muscarinic receptors in the SA node. Stimulation of these receptors results in bradycardia by increasing the polarity of these cells in the SA node. Therefore, the sympathovagal balance of the SA node should affect If channel activity. Ivabradine did not change the sympathovagal balance, despite significant slowing of the HR.
The main adverse effects of ivabradine are luminous phenomena (mainly a sensation of enhanced brightness with a fully maintained visual field), sinus bradycardia, first-degree atrioventricular blocks, ventricular extra systoles, dizziness, and/or blurred vision. Ivabradine is contraindicated in sick sinus syndrome and should not be taken concomitantly with CYP3A4 inhibitors.
Erythropoietin stimulates red cell production and increase the red cell mass and blood volume. Treatment with Erythropoietin is reserved for people with refractory symptoms in spite of other medications. Cost and administration by subcutaneous injection are the limiting factors for its use.
Pyridostigmine is an acetylcholine esterase inhibitor and is a very promising drug particularly for POTS following viral illness and POTS secondary to autoimmune process and paraneoplastic syndrome.
Anticipatory guidance to patients:
Make all postural changes from lying to sitting or sitting to standing, slowly.
Drink to 2.0 -2.5 L of fluids per day.
Increase sodium in the diet to 3 - 5 g per day. Performing 24 h urinary collection for urinary sodium level would help to identify the patients who would benefit from salt supplements. Studies show that patients with urinary excretion <124 mmol/d is an indicator of good response to salt treatment.
Avoid large meals which can cause low blood pressure during digestion. It is better to eat smaller meals more often than three large meals.
Avoid alcohol. Alcohol and cause blood to pool in the legs which may worsen low blood pressure reactions when standing. This can aggravate POTS.
Perform lower extremity exercises to improve strength of the leg muscles. This will help prevent blood from a pooling in the legs when standing and walking.
Raise the head of the bed by 6 to 10 inches. The entire bed must be at an angle. Raising only the head portion of the bed at waist level or using pillows will not be effective. Raising the head of the bed will reduce urine formation overnight and there will be more volume in the circulation in the morning.
During bad days, drink 500 cc of water quickly. This will result in an increased blood pressure within 5 minutes of drinking the water. The effect will last up to one hour and may improve orthostatic intolerance.
Use custom fitted elastic support stockings. These will reduce a tendency for blood to pool in the legs when standing and may improve orthostatic intolerance.
Use physical counter maneuvers such as leg crossing, squatting, or raising and resting the leg on a chair. These maneuvers increase blood pressure and can improve orthostatic intolerance.
Non-neurogenic causes: hypovolemia, cardiac failure, chronic illness with deconditioning and medication side-effects.
Medications causing orthostatic hypotension by impairing sympathetic tone:
Diuretics, anti-HTN, nitrates, arterial vasodilators
Sildenafil, CCB, phenothiazines, opiates, L-dopa, alcohol, TCA.
Neurogenic causes: failure of autonomic nervous system, neurodegenerative diseases (PD, PAF, DLB, MSA), peripheral neuropathies (diabetes), autoimmune disorders.
The clinical features should be established, with emphasis on precipitating factors, posture, type of onset of the faint (including whether it was abrupt or gradual), position of head and neck, the presence and duration of preceding and associated symptoms, duration of loss of consciousness, rate of recovery, and sequelae. Whether patient has fainted or fallen before. If possible, question an observer about clonic movements, color changes, diaphoresis, pulse, respiration, urinary incontinence, and the nature of recovery.
In the elderly, syncope may cause unexplained falls lacking prodromal symptoms.
Prodrome or symptom complex characterized by lightheadedness, generalized muscle weakness, giddiness, visual blurring, tinnitus, and GI symptoms (nausea, vomiting). Pt. may appear pale, diaphoretic, and cold.
In children prodromal symptoms may include hyperventilation.
In young women ask for history of basilar migraine.
Did the patient actually lose consciousness?
How fast was the loss of consciousness?
The onset of LOC is usually gradual in syncope, but can be rapid if it is related to conditions like cardiac arrhythmia.
Does the patient remembers the event?
Factor precipitating a syncopal episode: emotional stress, unpleasant visual stimuli, prolonged standing, or pain.
Vital signs?
Bradycardia = vasovagal event.
Was the patient standing, sitting or lying down when the attack occurred?
Syncope that occurred while the patient was in a recumbent position is a commonly seen in cardiac etiologies.
Syncope that occurs immediately after standing up suggest orthostatic hypotension or vasodepressor syncope
Dyautonomia, hypovolemia, decreased venous return
Ask the patient if he or she had fainted or fallen before?
Are there symptoms that he or she experiences when standing gets better on sitting or laying down?
Does the patient ever feel shoulder and neck pain or aching when standing up?
Precipitating by exertion:
Cardiac etiology: AS, HOCM.
Cerebrovascular disease
Aortic arch disease
Congenital heart disease
Takayasu disease
Pulmonary HTN
Anemia
Hypoxia
Hyperglycemia
Any seizure-like activity?
Brief seizure-like activity or myoclonic jerks may be seen in syncope. GTC is never seen in syncope. It is a seizure.
Urinary incontinence is uncommon.
Did the patient sustain any injury from the fall?
How fast the patient recovers?
Fainting episode corrects itself. As the patient becomes horizontal, normal color returns, breathing becomes more regular, and the pulse and BP return to normal.
Pt. may experience some weakness, but not postictal state.
Has this ever happened before? If so has a diagnosis being made to the previous attack?
Frequency of the spells?
Recurrent syncope in older patients indicates high likelihood of cardiavascular or cerebrovascular disease.
Exercise induced syncopal episodes: cardiac etiology (arryhthmias, AS, aortic arch disease, CHD, Takayasu disease, pulmonary HTN), cerebrovascular disease, anemia, hypoxia, hyperglycemia, dysautonomias, and situational syncope.
Are all episodes similar or some are different?
Is there any history of cardiac disease, seizure, stroke, or TIA?
Feeling recently ill? Ask about symptoms of infection, diarrhea, peptic ulcer, chest pain, palpitations, or neurologic dysfunction which would point to a predisposing illness.
Medications?
FH: SCD especially in females, suggest short QT-interval syndrome. Brugada syndrome
Medications, OTC, herbal remedies.
Any prior w/up, images, MRI, EEG, TTE, ECG, Holter, table-tilt, carotid doppler, MRA.
Have the patient lay supine for at least 5 minutes before checking the BP and HR, and then should be standing for at least 3 minutes to evaluate the BP.
Usually SBP rises on standing and the pulse rate increases.
Orthostatic hypotension: drop in >20 mmHg SBP, or >10 mmHg DBP within 3 minutes of standing. Patient assumes a standing position after laying supine for 5 minutes. BP and pulse is recorded from 1 to 5 minutes.
Measuring Orthostatic blood pressure:
Have the patient lie down for 5 minutes.
Measure and record blood pressure and pulse rate.
Have the patient sit for 1 to 2 minutes.
Measure and record blood pressure and pulse rate.
Have the patient stand for 1 to 2 minutes (standby patient for safety).
Measure and record blood pressure and pulse rate.
A drop in blood pressure of more than 20 mmHg, or end-diastolic blood pressure of more than 10 mmHg, or experiencing lightheadedness or dizziness is considered abnormal.
Pulse is usally slow, breathing is shallow. BP is low.
Check BP in both arms, when suspecting Takayasu arteritis, subclavian steal, cerebrovascular disease.
Patients with postural tachycardia syndrome (POTS - HR increased by 30/min from supine to standing, or persistent >120/min) frequently experience orthostatic symptoms without orthostatic hypotension, but syncope can occur occasionally. There is usually sympathetic activation in this syndrome.
During neurally mediated syncope, parasympathetic (vagal) outflow to the sinus node of the heart increases, producing bradycardia. Bradycardia, however, is not the main cause of the fall in blood pressure, because preventing the bradycardia by implantation of a pacemaker or administration of atropine does not avert syncope. Blood pressure falls because of vasodilation the mechanisms of which are not well understood.
Normal exam following recovery.
Tachycardia/bradycardia: dysrhythmia
HR >140 indicates an ectopic cardiac rhythm
HR <40 suggests complete AV block
Tachycardia, tachypnea, pleuritic CP: PE
Skin for pallor, diaphoresis, delayed capillary refill: low perfusion state.
HEENT: Check for trauma. Tongue laceration especially at the lateral borders seen in seizures.
Neck: Check for tenderness, step off. JVD. Carotid bruits
CVS: Heart murumur, irregular rhythm. pericardial rub.
Abdomen: pulsatile AAA, bruits. Heme-positive stool.
Genitourinary: Urinary incontinence and seizure
Rectal: blood, sphincter tone.
Extremities: Palpate for evidence of fracture.
Female patient with abdominal pain and vaginal bleeding in association with syncope needs a pelvic exam to check for the possibility of ectopic pregnancy.
Neuro exam to check for CNS lesion as a cause of syncope. Funduscopy to check for any subhyaloid hemorrhage seen in subarachnoid hemorrhage.
Lethargy, confusion, or disorientation: seizure, subarachnoid hemorrhage.
Hemianopia or aphasia-stroke, CNS mass lesion.
Diplopia, nystagmus, facial weakness or numbness, dysarthria, or dysphonia-vertebrobasilar and ischemia.
Hemiparesis/pronator drift: Todd's paralysis, stroke, CNS mass lesion.
Cogwheel rigidity: Shy-Drager syndrome.
Stocking-glove sensory loss and areflexia are peripheral autonomic neuropathy.
Appendicular or gait ataxia: vertebrobasilar ischemia.
Blood sugar, CBC, CMP, cardiac troponin, TSH, RPR, LFTs, ECG.
CXR
Urine and serum drug screen.
Tilt-table testing considered in patients with recurrent syncope in the absence of structural heart disease.
Head tilt is performed with an automated tilt table.
Patients should abstain from taking any medications for at least 12 hours (preferable 24 hrs) before testing, and should not eat within 2 hours of testing.
Baseline BP and HR are continuously recorded for 5 min in the supine position.
Patient is tilted up to 80° for at least 5 min.
If patient has a history of syncope patient is kept in the tilted up position at 80° for more prolonged periods for upto 45 minutes.
Caution: False positive can occur and at least 10% of normal persons may faint.
Specificity: 90%, sensitivity is highly variable.
Upright tilt table evaluation is used to obtain objective measures of blood pressure and heart rate in various postures.
In normal individuals, during the tilt table test, at 60 to 80 degrees of tilting for 10 minutes, the HR increases by 10-15 bpm, and the diastolic BP increases by 10 mmHg or more.
If there is a drop in SBP by 15 mmHg or in DBP by 10 mmHg, it is considered orthostatic hypotension.
If there is early, gradual, and sustained hypotension (>15 mm Hg reduction in systolic blood pressure) without compensatory tachycardia, this is an indication of insufficient sympathetic tone and impaired baroreceptor function (dysautonomia)
Hypotension with compensatory tachycardia suggests hypovolemia.
If hypotension is delayed for several minutes but then occurs abruptly with bradycardia, this is more suggestive of a neurocardiogenic mechanism. Most neurogenic causes of syncope lead to gradual hypotension without a compensatory tachycardia that occurs within the first 5 to 10 minutes of tilting.
Patients with postural tachycardia syndrome (POTS - HR increased by 30/min from supine to standing, or persistent >120/min)
Method: HUT is a method to simulate a prolonged passive stand without the active contraction of the calf muscles and is aimed to reproduce the pooling in the lower extremities that occurs upon standing. The patient lies flat on
the tilt table; HR is monitored with ECG and BP is monitored continuously both with a photoplethysmographic device and manually. Baseline measurement is obtained after 30 minutes of recumbence. The table is then tilted up rapidly at 60° to 80° for various periods of time, according to the clinical question to be addressed. For patients with autonomic failure and OH, the test duration is typically 5 minutes, as patients typically develop OH within 3 minutes. For patients with suspected POTS, test duration is extended to 10 minutes, as some patients may develop delayed hypotension. For patients with suspected reflex (neurally mediated, vasovagal) syncope, the test duration typically is 20 to 45 minutes followed by the administration of a provocative agent, typically intravenous isoproterenol (a beta adrenergic agonist that increases cardiac contractility and elicits vasodilation) or nitroglycerin (a potent venodilator).
Normal and Abnormal Responses: In normal conditions, the net effect of assuming the upright posture is a 10 to 20 beat-per-minute increase in HR, negligible changes in systolic BP, and an approximate 5 mm Hg increase of diastolic BP. The initial BP decrement is modest (less than 10 mm Hg of mean BP), with recovery within 1 minute. There are three main patterns of abnormal responses during HUT:
Neurogenic orthostatic hypotension (OH) is characterized by a fall of systolic BP ≥ 20 mm Hg and/or diastolic BP ≥ 10 mm Hg within 3 minutes of HUT.
Postural tachycardia syndrome (POTS) is defined by an HR increase ≥ 30 beats per minute and/or HR ≥ 120 beats per minute with standing.
Reflex (neurally-mediated, vasovagal) syncope is characterized by an initially stable (or slightly increased) BP and HR followed by a sudden drop of BP (vasodepressor response) and HR (cardioinhibitory response).
The first pattern is typical neurogenic OH characterized by a fall of systolic BP ≥ 20 mm Hg and/or diastolic BP ≥ 10 mm Hg within 3 minutes of standing or HUT. Neurogenic OH is typical of autonomic failure and is mainly the consequence of impaired sympathetically mediated reflex vasoconstriction. In these patients, the HR response is typically attenuated, but may be intact or even increased if cardiac sympathetic innervation is preserved. OH contrasts to indices of mild adrenergic impairment which include excessive oscillations of BP; an excessive decrease (>50 percent) of pulse pressure; a transient (less than 1 min) decrease in BP; or excessive increment of HR (> 30 beats per min). A variant called “delayed OH” may occur in some patients.
The second pattern is exaggerated and symptomatic orthostatic tachycardia which indicates POTS. This is defined by an HR increase ≥ 30 beats per minute and/or HR ≥ 120 beats per minute with standing. These criteria are applicable to patients older than 19 years of age; for younger patients, a 40 beats per minute HR increase is considered the cutoff point. POTS is multifactorial and may result from selectively impaired adrenergic vasoconstriction resulting in venous pooling (neuropathic POTS), hyperadrenergic state (hyperadrenergic POTS), as well as hypovolemia, and deconditioning, in various combinations.
The last pattern is reflex (neurally mediated, vasovagal) syncope, in which an initially stable (or slightly increased) BP and HR is followed by a sudden drop of BP (vasodepressor response) and HR (cardioinhibitory response). The mechanisms are poorly defined. It is due to an abrupt decrease in cardiac output and peripheral resistance triggered by activation of ventricular or other receptors.
TTE
Holter monitoring.
Plasma aldosterone, serum cortisol levels.
EP studies, cardiac stress testing, coronary angiography, chest CT angiogram or ventilation perfusion scan.
AAN recommends carotid imaging not be performed unless there are other focal neurologic symptoms:
Carotid doppler U/S
MRI, MRA of head and neck
Cerebral angiography is sometimes useful.
EEG
Cardiac cine MRI provide an alternative noninvasive modality that may be useful for patient in whom diagnostic-quality echocardiographic images cannot be obtained. Also, this test is useful for patients who have right ventricular outflow tract ventricular tachycardia, since the right ventricular structural abnormalities are better visualized better on MR imaging done by echocardiogram.
If a neurologic cause of syncope as suggested by history or examination, specific testing may include the following:
3 minute trial of hyperventilation, EEG without sleep, head CT or MRI, transcranial Doppler ultrasound to check intracranial vertebral and basilar arteries, duplex doppler ultrasonography, MRA or CTA, cerebral angiography, EMG/NCS.
HRCT, V/Q scan, or pulmonary angiography indicated in patients with syncope that maybe due to pulmonary embolus.
Doppler ultrasound studies of the carotid, MRI of the brain MRA of the head and neck without without contrast in patient with possible cerebrovascular syncope.
Obtain a fingerstick blood glucose level. Administer IV D5W. Place the patient onto the left side. Order a stat Foley ECG and rhythm strip.
The treatment of orthostatic hypotension is approached by nonpharmacological means and with pharmacological treatments.
Nonpharmacological approaches would include compression stockings or an abdominal binder.
Other approaches include volume-expanding agents such as increased salt intake or fludrocortisones acetate.
Erythropoietin can also expand blood volume, but its longterm safety and efficacy for this indication has not been established.
Nonetheless, volume-expanding agents would be contraindicated in a person with supine hypertension who is also being treated for essential hypertension. Midodrine is an alpha-agonist that has been known to worsen supine hypertension as noted in this patient. In contrast, pyridostigmine bromide has been shown to have efficacy in patients with both orthostatic hypotension and coexisting supine hypertension.
A population-based CAMERA (Cerebral Abnormalities in Migraine, an Epidemiologic Risk Analysis) study demonstrated an elevated prevalence of syncope and orthostatic intolerance in migraineurs without clear interictal signs of autonomic nervous system dysfunction. NEUROLOGY 2006;66:1034–1037