Syncope and presyncope

Syncope is transient loss of consciousness caused by global cerebral hypoperfusion, with rapid onset, short duration (usually under a minute) and spontaneous, complete recovery. Presyncope is the sensation of impending loss of consciousness (lightheadedness, visual dimming, muffled hearing, weakness, nausea, sweating) without loss. This article addresses the cardiovascular evaluation of true and impending syncope: recognising the mechanism, stratifying risk, and directing monitoring and therapy.

Clinical relevance. Syncope is responsible for about 1% to 3% of emergency visits and 1% of admissions, and about 35% of people have one event in a lifetime. Reflex syncope is benign and commonest; orthostatic syncope is commonest in older adults; cardiac syncope is less frequent (about 10% to 20%) but carries high risk of death and recurrence.

Classification by mechanism.

• Reflex (neurally mediated): vasovagal (emotional or orthostatic trigger), situational (cough, micturition, defaecation, swallowing, post exercise), carotid sinus syndrome, atypical forms.
• Orthostatic hypotension: drug induced, volume depletion, primary and secondary autonomic failure.
• Cardiac arrhythmic: sinus node dysfunction, atrioventricular block, supraventricular tachycardia, ventricular tachycardia, inherited channelopathies, device malfunction, proarrhythmic drugs.
• Cardiac structural and cardiopulmonary: aortic stenosis, hypertrophic cardiomyopathy, acute myocardial infarction, pulmonary embolism, pulmonary hypertension, aortic dissection, cardiac tamponade, atrial myxoma, prosthetic valve thrombosis.

Mechanism. Loss of consciousness follows a fall in systolic arterial pressure under about 60 mmHg or cessation of cerebral blood flow for 6 to 8 seconds. Vasovagal syncope involves sympathetic withdrawal and vagal excess, giving vasodilatation and bradycardia.

Syncope mimics (transient loss of consciousness without hypoperfusion). Epileptic seizure, psychogenic pseudosyncope, hypoglycaemia, hypoxia, intoxication, concussion, cataplexy, vertebrobasilar transient ischaemic attack. These are separate from syncope though they cause collapse.

History (patient and witness).

• Position and activity (cardiac causes): sitting or lying.
• Vasovagal: standing for long periods or after heat. Orthostatic: within 3 minutes of standing.
• During exertion: structural obstruction, channelopathy. Immediately after exertion: reflex or autonomic.
• With head turning or neck pressure: carotid sinus. With cough, micturition or swallowing: situational. With arm exercise: subclavian steal.
• During swimming: long QT syndrome type 1. Startle or alarm clock: long QT syndrome type 2.
• Prodrome: nausea, sweating, warmth, pallor, tunnel vision, yawning (reflex); palpitations (arrhythmia); none or brief (arrhythmia); chest pain or breathlessness (ischaemia, embolism); headache, neck pain (subarachnoid haemorrhage); tearing pain (dissection).
• Event: duration, colour (pale or blue), injury, tongue biting, incontinence, convulsive jerks (brief, after falling, in 10% of syncope), eye position.
• Recovery: quick and orientated (syncope); prolonged confusion or headache (seizure).
• Past history: structural heart disease, heart failure, arrhythmia, previous syncope (number, injury), diabetes, neurological disease, psychiatric illness, anaemia, pregnancy.
• Family history: sudden death under 50, cardiomyopathy, long QT syndrome, Brugada syndrome, pacemaker, unexplained drowning or road accident.
• Drugs: antihypertensives, diuretics, vasodilators, nitrates, alpha blockers, beta blockers, calcium channel blockers, digoxin, antiarrhythmics, tricyclics, insulin, alcohol, cocaine, phosphodiesterase inhibitors.
• QT prolonging drugs: macrolides, fluoroquinolones, antipsychotics, ondansetron, methadone.

Examination.

• Blood pressure and heart rate supine and at 1 and 3 minutes standing. A drop of 20 mmHg systolic or 10 mmHg diastolic, or systolic under 90 mmHg, is orthostatic hypotension. Postural orthostatic tachycardia syndrome is a rise of 30 beats/minute or more without hypotension.
• Also: blood pressure in both arms; oxygen saturation; temperature; glucose.
• Cardiac: rhythm, murmurs (aortic stenosis, hypertrophic cardiomyopathy, mitral stenosis), third heart sound, signs of right heart strain, jugular venous pressure, carotid bruits, prosthetic valve sounds.
• Carotid sinus massage (5 to 10 seconds, supine then upright, with ECG and blood pressure monitoring) if age over 40 and no bruit or recent stroke.
• Neurological: focal signs, gait, tremor, rigidity, cognition.
• Rectal examination for occult bleeding; abdominal mass.
• Injury assessment.

Red flags (high risk features).

• Exertional syncope; syncope when supine; syncope without prodrome or with brief palpitations beforehand.
• Chest pain, breathlessness, severe headache, abdominal or back pain.
• Known heart failure, structural disease, previous myocardial infarction, low ejection fraction.
• Family history of sudden death under 50.
• ECG abnormalities: bifascicular block, QRS 120 ms or more, Mobitz II or third degree block, sinus bradycardia under 40 or pauses over 3 seconds, pre-excited QRS.
• Further ECG abnormalities: QTc over 450 ms in men or 460 ms in women (short QT under 340 ms), Brugada pattern, epsilon waves, negative T waves in right precordial leads, Q waves, non sustained ventricular tachycardia.
• Systolic blood pressure under 90 mmHg, haemoglobin under 90 g/L, positive stool occult blood or evidence of haemorrhage.
• Age over 60 with comorbidity, recurrent syncope, injury.

Reflex syncope. Vasovagal, situational (micturition, defaecation, cough, swallow, post exercise), carotid sinus syndrome, glossopharyngeal neuralgia, triggers of pain, blood or instrumentation.

Orthostatic hypotension and autonomic failure. Drug induced, volume depletion (haemorrhage, dehydration, diabetes insipidus, adrenal insufficiency), autonomic neuropathy (diabetes, amyloid, alcohol, vitamin B12 deficiency, paraneoplastic), primary autonomic failure (pure autonomic failure, multiple system atrophy, Parkinson disease, Lewy body dementia).

Arrhythmias. Sinus node dysfunction, atrioventricular block, supraventricular tachycardia, atrial fibrillation with rapid or slow response, ventricular tachycardia, long QT syndrome (congenital and acquired), short QT syndrome, Brugada syndrome, catecholaminergic polymorphic ventricular tachycardia, arrhythmogenic right ventricular cardiomyopathy, device malfunction.

Structural and cardiopulmonary. Aortic stenosis, hypertrophic cardiomyopathy, mitral stenosis, atrial myxoma, prosthetic valve thrombosis, dilated cardiomyopathy, myocardial infarction, pulmonary embolism, pulmonary hypertension, aortic dissection, tamponade, coronary anomaly, congenital heart disease (Eisenmenger syndrome, tetralogy of Fallot).

Mimics. Seizure, hypoglycaemia, vertebrobasilar ischaemia, subclavian steal, subarachnoid haemorrhage, psychogenic pseudosyncope, hyperventilation, intoxication, cataplexy.

1. History, witness account, orthostatic blood pressure and ECG establish a cause in about 50% and guide risk. Obtain a 12 lead ECG for every patient.
2. Risk stratification: San Francisco Syncope Rule (congestive heart failure, haematocrit under 30%, ECG abnormal, shortness of breath, systolic blood pressure under 90 mmHg), Canadian Syncope Risk Score, or EGSYS score. Any high risk feature indicates admission for monitoring and evaluation.
3. Blood tests: full blood count, urea, creatinine, electrolytes, glucose, troponin if chest pain or ECG changes, natriuretic peptide, D-dimer or CT pulmonary angiography if embolism is possible, pregnancy test, cortisol, drug and alcohol screen as indicated.
4. Echocardiography for abnormal ECG, murmur, suspected structural disease or heart failure; cardiac MRI for cardiomyopathy.
5. Rhythm monitoring chosen by how often events occur: in hospital telemetry for high risk; Holter for daily events; external loop recorder for events at least monthly; implantable loop recorder (battery 3 years) for infrequent events with recurrent unexplained syncope.
6. Autonomic testing: active standing for 3 minutes, tilt table testing (60 to 70 degrees for 20 minutes then glyceryl trinitrate 400 micrograms sublingually for a further 15 minutes) when reflex syncope is suspected but not established; carotid sinus massage; Valsalva manoeuvre and deep breathing.
7. Exercise testing for syncope on exertion; coronary angiography if ischaemia; electrophysiology study for bundle branch block with syncope or after myocardial infarction with ventricular scar.
8. Genetic testing and family screening for channelopathies and cardiomyopathies; ajmaline challenge for suspected Brugada syndrome in specialist centres.
9. Brain imaging, electroencephalography and neurological assessment only when seizure or focal signs raise suspicion.
10. Syncope units or structured clinic assessment for recurrent unexplained syncope. Psychiatric evaluation for suspected pseudosyncope.

Limits. Tilt testing has variable sensitivity and specificity, and a positive test does not exclude a cardiac cause. Loop recorders may record asymptomatic arrhythmia that is not the cause. No cause is found in 20% to 30%.

Resuscitation and acute care. Lay flat with legs raised, check airway, breathing, circulation, glucose and rhythm. Treat life threatening causes at once:

• pulmonary embolism: anticoagulation, thrombolysis for shock with alteplase 100 mg over 2 hours
• aortic dissection: labetalol, surgery
• acute coronary syndrome: aspirin 300 mg, antiplatelet, anticoagulation, reperfusion
• haemorrhage: blood and source control
• ventricular arrhythmia: cardioversion, amiodarone
• bradycardia: atropine 500 micrograms intravenously repeated to 3 mg, pacing

Reflex syncope.

• Explanation and reassurance; recognise early symptoms and sit or lie down.
• Physical counter pressure manoeuvres (leg crossing with muscle tensing, hand grip, arm tensing) at onset.
• Avoid triggers (prolonged standing, heat, dehydration, large meals, alcohol).
• Fluids 2 to 3 litres and salt 6 to 10 g daily if blood pressure is low and no hypertension.
• Reduce or stop hypotensive drugs.
• Tilt training (standing against a wall for increasing durations) is of limited value.

Recurrent severe cases: midodrine 2.5 to 10 mg three times daily (last dose before 6 pm; avoid supine hypertension), or fludrocortisone 100 to 200 micrograms daily (monitor potassium and blood pressure).

Cardiac pacing is an option for documented cardioinhibitory syncope in older patients (over 40) with pauses of 3 seconds or more with symptoms. Beta blockers are not effective.

Orthostatic hypotension.

• Stop or reduce offending drugs.
• Fluid 2 to 3 litres daily, salt 6 to 10 g daily.
• Compression stockings (30 to 40 mmHg thigh high) and abdominal binders; head up sleeping at 10 to 20 degrees; slow staged standing.
• Avoid large meals, alcohol and heat.
• Midodrine 2.5 to 10 mg three times daily or fludrocortisone 100 to 300 micrograms daily.
• Droxidopa 100 to 600 mg three times daily where available; pyridostigmine 30 to 60 mg two to three times daily as an alternative.

Cardiac syncope.

• Bradyarrhythmia: permanent pacemaker (dual chamber for atrioventricular block).
• Tachyarrhythmia: catheter ablation (supraventricular tachycardia, flutter, some ventricular tachycardia); antiarrhythmic drugs; implantable cardioverter defibrillator for ventricular tachycardia or fibrillation, reduced ejection fraction (35% or less), and high risk channelopathy or cardiomyopathy.
• Long QT syndrome: avoid QT prolonging drugs and hypokalaemia; beta blocker (nadolol 1 to 2 mg/kg daily or propranolol 2 to 4 mg/kg daily); left cardiac sympathetic denervation; implantable cardioverter defibrillator.
• Brugada syndrome: avoid provoking drugs, treat fever with paracetamol 1 g, implantable cardioverter defibrillator for syncope or arrhythmia; quinidine as an adjunct.
• Catecholaminergic polymorphic ventricular tachycardia: nadolol 1 to 2 mg/kg daily, flecainide 100 to 150 mg twice daily, and implantable cardioverter defibrillator.
• Hypertrophic cardiomyopathy: avoid exertion and dehydration; metoprolol succinate 50 to 200 mg daily or verapamil; septal myectomy or alcohol ablation; implantable cardioverter defibrillator by risk score.
• Aortic stenosis: aortic valve replacement for symptomatic severe stenosis.
• Pulmonary hypertension: specialist care.

Driving, occupation and advice. Do not drive until the cause is found and treated. Reflex syncope with clear prodrome and a single event may allow early return. Unexplained or cardiac syncope needs restriction (commonly 4 weeks to 6 months, longer for commercial or heavy goods drivers) as set by local law. Avoid working at heights or operating dangerous machinery until controlled.

Disposition.

• Admit: high risk features, structural heart disease, abnormal ECG, exertional or supine syncope, severe anaemia or bleeding, pulmonary embolism, injury, or inability to arrange follow up.
• Discharge: typical reflex or orthostatic syncope, normal examination and ECG, low risk, with advice and follow up.

Monitoring. Telemetry for 24 to 48 hours in high risk; review at 1 to 2 weeks with monitor results; repeat orthostatic blood pressure after drug changes; pacemaker and defibrillator follow up.

Referral and escalation. Cardiology or electrophysiology for suspected cardiac syncope; syncope unit for recurrent unexplained syncope; neurology or autonomic service for autonomic failure; geriatrics for older adults with falls; psychiatry for functional episodes.

Safety netting. Return at once for further fainting, injury, palpitations, chest pain, breathlessness, severe headache, black stool, or weakness on one side.

Special groups.

• Children and adolescents: usually vasovagal; exertional syncope, family history of sudden death and abnormal ECG need cardiac evaluation.
• Athletes: exertional syncope needs full cardiac evaluation before return to sport; post exertion syncope is often benign.
• Pregnancy: supine hypotensive syndrome, vasovagal syncope; exclude pulmonary embolism, peripartum cardiomyopathy and ectopic pregnancy.
• Older adults: multifactorial; stop unnecessary drugs, check orthostatic pressure, and consider carotid sinus hypersensitivity. Falls without recall of syncope are common.
• Endemic regions: Chagas cardiomyopathy, rheumatic valve disease, severe anaemia and dehydration.