Syncope Teresa Menendez Hood, M.D.

Definition Syncope is a symptom in which there is transient (<30 secs) and self-limited loss of consciousness usually leading to a fall. The onset is rapid and recovery is spontaneous, complete and prompt. The underlying mechanism is relatively abrupt cerebral hypoperfusion.The onset may or may not have warning and some older patients may have retrograde amnesia. Fatigue is common post- syncope. Syncope is a symptom in which there is transient (<30 secs) and self-limited loss of consciousness usually leading to a fall. The onset is rapid and recovery is spontaneous, complete and prompt. The underlying mechanism is relatively abrupt cerebral hypoperfusion.The onset may or may not have warning and some older patients may have retrograde amnesia. Fatigue is common post- syncope.

SYNCOPE STATS 25% people will have syncope at some point 25% people will have syncope at some point 6% of hospital admits are for syncope 6% of hospital admits are for syncope 3% of all ER visits 3% of all ER visits 30% have recurrences 30% have recurrences 40% remain undiagnosed after initial evaluation 40% remain undiagnosed after initial evaluation

Syncope: Etiology Orthostatic Cardiac Arrhythmia Structural Cardio- Pulmonary * Non- Cardio- vascular Neurally- Mediated Unknown Cause = 34% 24% 11% 14% 4% 12%

Causes of Syncope Neurally-mediated reflex syncope-a reflex that when triggered gives rise to vasodilation and/or bradycardia Neurally-mediated reflex syncope-a reflex that when triggered gives rise to vasodilation and/or bradycardia Vasovagal -look for precipitating events: fear, pain, prolonged standing Vasovagal -look for precipitating events: fear, pain, prolonged standing Carotid sinus -turning head to one side, age >40 Carotid sinus -turning head to one side, age >40 Situational -cough, micturition, post-exercise, post-prandial, swallow, defecation…. Situational -cough, micturition, post-exercise, post-prandial, swallow, defecation….

Causes of Syncope Orthostatic Orthostatic Autonomic Failure- the autonomic nervous system does not work well and one does not get the vasoconstrictor mechanisms to upright posture : Autonomic Failure- the autonomic nervous system does not work well and one does not get the vasoconstrictor mechanisms to upright posture : primary or multisystem, secondary (DM, amyloid), drug induced (the most common). Look for autonomic problems in other organs..i.e cannot sweat, impotence, disturbed micturition primary or multisystem, secondary (DM, amyloid), drug induced (the most common). Look for autonomic problems in other organs..i.e cannot sweat, impotence, disturbed micturition Volume depletion Volume depletion Cardiac Arrhythmias Cardiac Arrhythmias Sinus node dysfunction, AVN disease, SVT/VT, inherited diseases(LQT, Brugada, WPW,ARVD,HCM) Sinus node dysfunction, AVN disease, SVT/VT, inherited diseases(LQT, Brugada, WPW,ARVD,HCM)

Causes of Syncope Structural Cardiac or Cardiopulmonary disease- an obstruction of blood flow Structural Cardiac or Cardiopulmonary disease- an obstruction of blood flow Valvular disease Valvular disease Obstructive CM Obstructive CM Atrial Myxoma Atrial Myxoma Aortic dissection Aortic dissection Tamponade Tamponade PE PE

Causes of Syncope Cerebrovascular Cerebrovascular Vascular steal syndrome -subclavian steal:rare, syncope associated with arm exercise: the blood vessel supplies both the brain and the arm. Check for BP in both arms! Vascular steal syndrome -subclavian steal:rare, syncope associated with arm exercise: the blood vessel supplies both the brain and the arm. Check for BP in both arms! Vetebrobasilar TIA -doubtful that can really cause syncope Vetebrobasilar TIA -doubtful that can really cause syncope

Features suggestive of cardiac causes? Occur in the supine position or during exertion Occur in the supine position or during exertion Preceded by palpitations Preceded by palpitations Presence of severe heart disease Presence of severe heart disease EKG abnormalities: wide QRS, AV conduction disease, Q waves, LQT, delta wave, SQT, epsilon wave EKG abnormalities: wide QRS, AV conduction disease, Q waves, LQT, delta wave, SQT, epsilon wave

Features suggestive of Neurally-Mediated causes? Prolonged standing in crowded, warm place Prolonged standing in crowded, warm place Preceding nausea, feeling cold and sweaty Preceding nausea, feeling cold and sweaty After exertion or post-prandial After exertion or post-prandial Tonic-clonic movements are short in duration and occur after the loss of consciousness Tonic-clonic movements are short in duration and occur after the loss of consciousness Long duration of symptoms …>4years Long duration of symptoms …>4years

Causes of non-syncopal attacks Impairment of /loss of consciousness Impairment of /loss of consciousness Metabolic-hypoglycemia, hypoxia, hyperventilation syndrome Metabolic-hypoglycemia, hypoxia, hyperventilation syndrome Epilepsy-Typical premonitory aura? Post-ictal state? Epilepsy-Typical premonitory aura? Post-ictal state? Loss of muscle control Loss of muscle control Cataplexy-usually with narcolepsy Cataplexy-usually with narcolepsy Psychogenic Psychogenic

The Initial Evaluation Careful History - from patient and witnesses: this is the most important tool in the diagnosis! Careful History - from patient and witnesses: this is the most important tool in the diagnosis! Prior to attack, onset, eyewitnesses, end of the attack, PMH, FH, drug history? Prior to attack, onset, eyewitnesses, end of the attack, PMH, FH, drug history? Physical exam- include orthostatic BP Physical exam- include orthostatic BP Standard EKG Standard EKG

Evaluation The use of EEG, CT, MRI, carotid dopplers are not usually helpful in the workup of syncope The use of EEG, CT, MRI, carotid dopplers are not usually helpful in the workup of syncope Hospitalize patients when the features suggest a cardiac cause, when it results in severe injury, or when the syncope is frequent Hospitalize patients when the features suggest a cardiac cause, when it results in severe injury, or when the syncope is frequent

Evaluation When the cause of the syncope is not evident after the initial evaluation and there is evidence of heart disease then the possibility of cardiac syncope must be entertained as these patients have a high mortality at one year(18-30% mortality) When the cause of the syncope is not evident after the initial evaluation and there is evidence of heart disease then the possibility of cardiac syncope must be entertained as these patients have a high mortality at one year(18-30% mortality) Cardiac evaluation: echo, stress test, holter/loop and EP testing. Cardiac evaluation: echo, stress test, holter/loop and EP testing. In a patient with cardiac disease but with negative cardiac workup, then proceed with tilt testing and / or implantable loop recorder. In a patient with cardiac disease but with negative cardiac workup, then proceed with tilt testing and / or implantable loop recorder.

Evaluation In those without heart disease, then tilt table testing and carotid massage (more important in the patients > 40) for neurally mediated syncope is recommended for those with recurrent or severe syncope. In those without heart disease, then tilt table testing and carotid massage (more important in the patients > 40) for neurally mediated syncope is recommended for those with recurrent or severe syncope. SAECG has fallen out of favor. If it is normal it helps. SAECG has fallen out of favor. If it is normal it helps.

Test/ProcedureYield (based on mean time to diagnosis of 5.1 months 7 History and Physical (including carotid sinus massage) 49-85% 1, 2 ECG 2-11% 2 Electrophysiology Study without SHD* 11% 3 Electrophysiology Study with SHD 49% 3 Tilt Table Test (without SHD) 11-87% 4, 5 Ambulatory ECG Monitors: Holter Holter 2% 7 External Loop Recorder External Loop Recorder (2-3 weeks duration) 20% 7 Implantable Loop Recorder Implantable Loop Recorder (up to 14 months duration) 65-88% 6, 7 Neurological † (Head CT Scan, Carotid Doppler) 0-4% 4,5,8,9,10

Patient ActivatorReveal ® Plus ILR9790 Programmer Offers up to 14 months of continuous, leadless ECG monitoring Offers up to 14 months of continuous, leadless ECG monitoring High diagnostic yield (65-88%) High diagnostic yield (65-88%) High patient compliance High patient compliance Patient and auto triggered to capture ECG Patient and auto triggered to capture ECG Reveal ® Plus ILR

Implant parallel to the midline in the region From left parasternal area to the mid-clavicular line First to the fourth rib Implant zone for optimal auto activation performance Implant zone for optimal auto activation performance

0.4 mV :45:44:43:42:41:40:39:38:37 :36:35:34:33:32:31:30:29 :28:27:26:25:24:23:22:21 08:23:2 1 8:23:29 08:23:3 7

Randomized Assessment of Syncope Trial (RAST) Comparison of the Implantable Loop Recorder with Conventional Diagnostic Testing for Unexplained Syncope 1 Andrew D. Krahn, George J. Klein, Raymond Yee, Allan C. Skanes University of Western Ontario London Ontario Canada 1. Krahn A, et al. Circ. 2001;104(11):46-51

Prospective randomized trial (60 patients with unexplained syncope referred for cardiac investigation) Inclusion: Recurrent unexplained syncope Referred to the arrhythmia service for cardiac investigation No clinical diagnosis after history, physical, ECG and at least 24 hours of cardiac monitoring Exclusion: LVEF < 35% Unable to give informed consent Major morbidity precluding 1 year of follow-up Methods

Conventional Investigations : ELR then HUT then EPS(see below for definitions) ILR 4 Left sided implant with antibiotics Patient education 1 year of follow-up Crossover After primary arm was completed, patients were offered crossover to facilitate diagnosis Methods 1.External loop recorder(ELR) 2.Head up tilt test(HUT) 3.Electrophysiological study(EPS) 4.Insertable Loop Recorder(ILR)

ILR (n=30) Conventional (n=30) Age (years)64 +/ /- 14 Gender (# male)19 (63%)14 (47%) Syncopal Episodes4.1 +/ /- 6.6 Duration of Syncope (yrs)6.6 +/ /- 2.7 LVEF (%)55 +/ /- 6 Results

RAST Results Randomized Assessment of Syncope Trial

RAST Crossover Results

Diagnosis By:ILR*Conventionalp value Primary Strategy14/27 (52%)6/30 (20%)p=0.012 Crossover8/13 (62%)1/6 (17%)p=0.069 Primary and Crossover22/40 (55%)7/36 (19%)p= * 3 primary ILRs and 8 crossover ILRs have not completed follow up. RAST Results

Conclusions This prospective randomized trial suggests that the implanted loop recorder has a superior diagnostic yield as a primary strategy. The diagnostic yield of conventional testing in these patients is disappointing (19%). The loop recorder retains high utility when used after conventional testing is negative. Consideration should be given to use at an earlier stage in the diagnostic cascade in this patient population.

AsystoleBrady Normal SR Tachy Syncope Recurrence Pilot study Circulation, 95 N/A 7 (47%) 6 (40%) 2 (13%) 15/16 94% Krahn et al Circulation, 99 N/A 14 (69%) 7 (30%) 2 (9%) 23/85 27% Nierop et al PACE, 2000 N/A 4 (29%) 6 (43%) 4 (29%) 14/35 40% ISSUE study Circulation, (50%) 3 (9%) 12 (34%) 1 (3%) 32/111 29% Total 44 52% 31 37% 9 11% 84/247 34%

Indications Patients with clinical syndromes or situations at increased risk of cardiac arrhythmias Patients with clinical syndromes or situations at increased risk of cardiac arrhythmias Patients who experience transient symptoms that may suggest a cardiac arrhythmia Patients who experience transient symptoms that may suggest a cardiac arrhythmia The Reveal Plus Insertable Loop Recorder is indicated for:

Tilt Table Diagnosis Neurocardiogenic-seen in 50% of patients with heart disease and 75% of patients without heart disease who present with syncope Neurocardiogenic-seen in 50% of patients with heart disease and 75% of patients without heart disease who present with syncope Type 1 mixed: bp falls before heart rate and the heart rate does not get 3 secs and heart rate falls at the time of syncope Type 1 mixed: bp falls before heart rate and the heart rate does not get 3 secs and heart rate falls at the time of syncope Type 2a: cardioinhibitory without asystole-bp falls before the heart rate and heart rate gets below 40 but no asystole > 3 secs Type 2a: cardioinhibitory without asystole-bp falls before the heart rate and heart rate gets below 40 but no asystole > 3 secs Type 2b: cardioinhibitory with asystole-heart rate falls below 40 for > 10secs and asystole is present >3 secs Type 2b: cardioinhibitory with asystole-heart rate falls below 40 for > 10secs and asystole is present >3 secs Type 3: pure vasodepressor-bp falls but heart rate does not fall >10% from peak heart rate. Type 3: pure vasodepressor-bp falls but heart rate does not fall >10% from peak heart rate.

Tilt Table Diagnosis Dysautonomic Dysautonomic Gradual decline in the systolic and diastolic bp with or without a drop in the heart rate. Gradual decline in the systolic and diastolic bp with or without a drop in the heart rate. Orthostatic intolerance is the key problem Orthostatic intolerance is the key problem POTS-Postural orthostatic tachycardia syndrome POTS-Postural orthostatic tachycardia syndrome An excessive heart rate response to maintain a low normal blood pressure. Will have an excess of >30 beats increase when placed upright An excessive heart rate response to maintain a low normal blood pressure. Will have an excess of >30 beats increase when placed upright

Tilt Table Diagnosis Cerebral syncope Cerebral syncope Associated with cerebral vasoconstriction in the absence of systemic hypotension and would need a transcranial Doppler for confirmation Associated with cerebral vasoconstriction in the absence of systemic hypotension and would need a transcranial Doppler for confirmation Psychogenic Psychogenic

Protocols Westminster Westminster Passive tilt for 45 minutes at degrees and has a positive rate of 75% with specificity of 95% Passive tilt for 45 minutes at degrees and has a positive rate of 75% with specificity of 95%

Protocols Italian Italian Passive tilt for 20 minutes and the challenge with SUBLINGUAL NITROGLYCERIN while still upright and has specificity of 94%. Passive tilt for 20 minutes and the challenge with SUBLINGUAL NITROGLYCERIN while still upright and has specificity of 94%. Will see a progressive drop in the BP with no bradycardia if the effect is due to the drug alone and this is not a positive test..seen in 20%! Will see a progressive drop in the BP with no bradycardia if the effect is due to the drug alone and this is not a positive test..seen in 20%!

Syncope History and Physical ECG Known SHD No SHD Echo EPS + Treat > 30 days; > 2 Events Tilt ILR Tilt Holter/ ELR ILR Tilt/ILR < 30 days -