EKG CONFERENCE Stress Testing and Ischemia...Engel GL. Psychologic stress, vasodepressor syncope,...
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Syncope Peter Netzler AnMed Health Arrhythmia Specialists February 22, 2014
Transcript of EKG CONFERENCE Stress Testing and Ischemia...Engel GL. Psychologic stress, vasodepressor syncope,...
SyncopePeter Netzler
AnMed Health Arrhythmia SpecialistsFebruary 22, 2014
Syncope
I have no disclosures1. Incidence and prevalence2. Broad differential3. Risk Stratification4. Work up and treatment for vasovagal syncope5. Conclusions
Syncope
Transient, abrupt, loss of consciousness, with rapid, usually complete, recovery, with or without a prodrome, caused by cerebral hypoperfusion
Derives from the Greek word synkoptein, meaning “to cut short”
A common, non-specific, alarming, debilitating, symptom with diverse causes and the key in making the diagnosis is in the History and Physical
Dilemma: Avoid over-testing yet avoid under-diagnosing life-threatening causes
1 Engel GL. Psychologic stress, vasodepressor syncope, and sudden death. Ann Intern Med 1978; 89: 403-412.
Presenter
Presentation Notes
“The same as sudden death except that you wake up”
Cause of Syncope* - Recent Data
Framingham Cohort – 727 patients*
*Soteriades ES et al. N Engl J Med 2002;347:878-885**Linzer M et al Ann Int Med 1997;126:989
Pooled Data Five Studies**
Cause Prevalence %Men Women
Vasovagal 19.8 22.2Orthostatic 8.6 9.9Cardiac 13.2 6.7Seizure 7.2 3.2Stroke/TIA 4.3 4.0Medication 6.3 7.2Other 9.5 6.1Unknown 31.0 40.7
*Full differential diagnosis beyond scope of talk
Cause %Vasovagal 18Situational 5Orthostatic 8Cardiac 18Medication 3Psychiatric 2Neurologic 10Carotid sinus 1Unknown 34
Presenter
Presentation Notes
There is such a broad differential with the preponderance being vasovagal or (neurocardiogenic) and cardiac. These are results from the Framingham cohort as well as pooled data from a meta analysis of 5 studies both showing high percentages of vasovagal, cardiac and the frustrating unknown.
SYNCOPE – Background
Syncope is common in the general population1
Syncope accounts for 3-5% of Emergency Department (ED) visits and 1-3% of all hospital admissions2,3
Not created equal Cardiac syncope doubled the
risk of death from any cause with a 6 mo mortality rate>10%4
Soteriades ES. N Engl J Med 2002;347:878-885
Presenter
Presentation Notes
Unfortunately, all sycnope is not created equal and there is a lot of it, accounting for 3-5% of all ED visits and 1-3% of hospital admits. Again looking at data from the Framingham heart study of the 7814 participants, 822 had syncope in the 17 year f/u. The black line represents no syncope. Vasovagal (the yellow line) was found to the most common cause at 21.2% and was not associated with increased risk of death however cardiac syncope (red line) was found in 9.5% and associated with a two fold increase in death, and a 6 month mortality rate >10%.
Syncope
Incidence: 500,000/year >1,000,000 evaluated annually 10% of falls due to syncope 10.2 visits/year, 3.2 specialists Cause for disability * * 20-50% of adults experience syncope at least
once in a lifetime
Impact on the Medical Community
*Krahn AD Am Heart Journal 1999;137:870**Linzer, J Clin Epidemiol, 1991;44:1037-43
Linzer, J Gen Int Med, 1994;9:181-6
Syncope: Economic Burden
Per recent data, the overall cost per hospital admission was estimated to be about $10,600.
One study found $17,000 of “unnecessary” testing to diagnosis vasovagal syncope
Overall cost in US estimated to be in excess of $1 billion.
Costs of Test Troponin $156 EKG $274 Telemetry $2,325/d Head CT $1901 MRI brain $3947 Carotid US $1294 EST $1156 Echocardiogram $1835 EEG $978
Syncope: Pathophysiology Common final pathway is
decreased cerebral perfusion Cessation of cerebral
perfusion for as little as 3-5 seconds can result in syncope
Decreased cerebral perfusion may occur as a result of decreased cardiac output or decreased systemic vascular resistance.
Syncope: Etiology
Orthostatic CardiacArrhythmia
StructuralCardio-
Pulmonary
*
1• Vasovagal• Carotid Sinus• SituationalCoughPost-
micturitionDefaecationSwallow
2• Drug Induced
• Volume Depletion
• ANSFailurePrimarySecondary
3• BradySick sinusAV block
• TachyVTSVT
• Inherited
4 • Aortic Stenosis• HOCM• PulmonaryHypertension
5• Psychogenic• Metabolic• Epilepsy• Intoxications• TIA• Falls
Non-Syncopal
Neurally-Mediated
Unknown Cause = 2%
66% 10% 11% 5% 6%
Brigole et al. Heart 2007;93:130-136
Presenter
Presentation Notes
This slide provides a simple classification of the principal causes of syncope. This scheme lists the causes of syncope from the most commonly observed (Left) to the least common (Right). This ranking may be helpful in thinking about the strategy for evaluating syncope in individual patients. Within the boxes,the most common causes of syncope are indicated for each of the major diagnostic groups. The numbers at the bottom of each column provide an approximate value for the average frequency (Kapoor 1998) with which that category appears in published reports summarizing diagnostic findings. It should be noted that orthostatic causes are not often referred to specialists and consequently tend to be under represented in the literature.
Cause of Syncope – By Age Younger patient
Neurocardiogenic Situational Psychiatric Long QT* Brugada’s syndrome* WPW syndrome* RV dysplasia* Hypertrophic
cardiomyopathy*
Older patient Cardiac**
Mechanical Arrhythmic
Orthostatic hypotension Drug-induced Neurally mediated Multifactorial
*infrequent but not benign **generally not benign
Underlined: generally benign
Presenter
Presentation Notes
Underlined diagnosis are generally benign
RISK STRATIFICATION
Etiology can be benign…or deadly…
that’s the rub… HISTORY alone identifies the cause up to 85% of
the time POINTS to CONSIDER
Previous episodes Character of the events, witnesses Events preceding the syncope Events during and after the episode
Short-Term High Risk Criteria Severe structural or CAD (CHF, low EF, prior MI) Clinical or EKG ->Arrhythmia
During exertion or supine Palpitations NSVT Bifascicular block Bradycardia Pre-excited QRS complex RBBB with ST elevation in V1-V3 (Brugada pattern) Long or short QT Negative T waves in right precordial leads, epsilon waves or ventricular
late potentials suggestive of ARVC Severe anemia Electrolyte disturbance
Presenter
Presentation Notes
These require prompt hospitalization or intensive evaluation and this was discussed last year
Risk Stratification‘Short-term’ Risk (1 week – 1 month)
Study Clinical Markers
San Francisco
Quinn JV, et al. Ann Emerg Med 2004;43:224.
Abnormal ECG, Low Blood Pressure, CHF, SOB,Hematocrit <30%
Rose rule
Reed MJ,et al. J Am Coll Cardiol. 2010;55:713
Abnormal ECG,Elevated BNP, Chest painFecal blood
StePs
Costantino G, et al.J Am Coll Cardiol 2008; 51:276-283
Abnormal ECG, Trauma, No warning, Male gender
Date of download: 2/22/2014
Copyright © The American College of Cardiology. All rights reserved.
From: The ROSE (Risk Stratification of Syncope in the Emergency Department) Study
J Am Coll Cardiol. 2010;55(8):713-721. doi:10.1016/j.jacc.2009.09.049
The ROSE Rule With “BRACES” Mnemonic Aide MemoireA patient should be considered high-risk and admitted if any of the 7 criteria in the ROSE (Risk stratification Of Syncope in the Emergency department) rule are present. BNP = B-type natriuretic peptide; ECG = electrocardiogram.
Figure Legend:
Syncope
History and Physical
ECG
KnownSHD
NoSHD
Echo
EPS
+
Treat
> 30 days; > 2 Events
Tilt ILR
Tilt Holter/ ELR
ILR
Tilt/ILR
< 30 days
-
Diagnostic Algorithm
Presenter
Presentation Notes
This flow chart shows a typical sequence of testing, patients may undergo in search of a diagnosis. Last year, my partner focused on syncope in the patient with mild heart disease including structural and moderately depressed systolic function patients. As we have seen, patients with cardiac syncope have a much higher morbidity and mortality and many will benefit from invasive EPS testing and defibrillators. What we are going to focus on more today is on the right of the screen and the patients without structural heart disease.
Neurological Tests Carotid Dopplers, EEG,
Head CT / MRI
• Little value in syncope evaluation• Imaging only if there is concern re
head injury from ‘fall’ or seizure• EEG only if seizure concern, but inter-
ictal EEG may be non-diagnostic • Neurological consultation is advised
prior to tests
Lower Risk Patient
Overall normal EKG??? Normal ECHO or no/little concern for
structural heart disease No high risk features
NEURALLY MEDIATED SYNCOPE
Vasovagal, carotid sinus, situational
Represents 66% of patients with syncope
No increased risk for cardiovascular morbidity or mortality associated with reflex mediated syncope.
Presenter
Presentation Notes
???? Maybe delete Figure 1 Overall survival of participants with syncope according to cause, and participants without syncope, among 7814 participants of the Framlingham heart study.
Features suggestive of Neurally-Mediated causes?
Prolonged standing in a crowded, warm place
Preceding nausea, feeling cold and sweaty After exertion or post-prandial Tonic-clonic movements are short in
duration and occur after the loss of consciousness
Long duration of symptoms …>4years
Tilt-Table Test Indications:
If a neurocardiogenic cause is suspected Recurrent syncope, no apparent cause, any age Other evaluation unrevealing Treating other potential causes ineffective
Do not tilt if etiology is clear or if tilt has dangers
1. Delepine S. Am J Cardiol 2002; 5:488-912. Raviele, A. Am J Cardiol 2000;85:1194-83. Calkins H. J Cardiovasc Electrophysiol 2001;12:797-9 4. Saadjian, A. Y Circulation 2002;106:569-74
Head-Up Tilt Test (HUT)
• Protocols vary some use provocative drugs Isuprel or nitrogylcerin
• Goals: Unmask VVS susceptibility Reproduce symptoms Patient learns VVS warning
symptoms Patient more confident of diagnosis
• Not recommended for predicting treatment benefit
Presenter
Presentation Notes
The rationale for undertaking head-up tilt (HUT) testing in patients suspected of having vasovagal (VVS) syncope is summarized here. In essence, the test may not only provide useful diagnostic information, but it also provides an opportunity for patients to become more familiar with the condition and its possible warning signs. The latter may prove to be of considerable diagnostic utility in many individuals. Provocative drugs: isoproterenol vs. sublingual nitroglycerin—Isoproterenol, nitroglycerin, adenosine sensitivity1-4 but may specificity
VVS: Typical HUT Protocols
• Basic Preparation 4 hour fast Continuous ECG monitor Continuous BP monitor
• Finometer® or equivalent preferred• Arterial line
• if placed >1 hour before
• Sphygmomanometer BP discouraged• disruptive to Autonomic Nervous system
Moya A et al, ESC Syncope Guidelines, Eur Heart J 2009; 30: 2631-71
Minimally Disruptive Beat-to beat BP
Presenter
Presentation Notes
Diagnosing VVS VVS is most effectively diagnosed if the detailed medical history is ‘classic’. However, this is not often the case, and supporting evidence is needed, Such supportive evidence may include: Patient history, physical examination, ECG, and other tests provide no diagnosis for patient complaints of syncope. Patient experiences syncope during head-up tilt-table testing. Test completion without syncope is a negative result. The following HUT protocol is based on the ACC Consensus Document on tilt-table testing (Benditt 1996). Other accepted HUT protocols do exist. Overnight fast, morning test ECG (at least 3 leads) Continuous blood pressure monitoring Patient remains supine on the table for 15-30 minutes. Tilt to 60-80 degrees for 20-45 minutes. Lower to horizontal and administer isoproterenol at 1-5 g/min until heart rate increases 25%. Re-tilt for 10 minutes� REFERENCE: Benditt DG, Ferguson DW, Grubb BP, et al. Tilt table testing for syncope. ACC Expert Consensus Document. JACC. 1996;28(1):263-275.
Typical HUT Protocol Supine rest period 5-20 min Tilt to 60-70°for 20 min Positive end-point: Syncope with reproduction of
symptoms If negative, then add drug provocation while still
upright• Nitroglycerine 0.4mg SL, or• Isoproterenol 1-5 mcg/min, to increase HR to 125%
baseline Extend tilt after drug, duration 10-15 minutes Test completion without syncope is a negative
resultMoya A et al, ESC Syncope Guidelines,
Eur Heart J 2009; 30: 2631-71
Presenter
Presentation Notes
Diagnosing VVS VVS is most effectively diagnosed if the detailed medical history is ‘classic’. However, this is not often the case, and supporting evidence is needed, Such supportive evidence may include: Patient history, physical examination, ECG, and other tests provide no diagnosis for patient complaints of syncope. Patient experiences syncope during head-up tilt-table testing. Test completion without syncope is a negative result. The following HUT protocol is based on the ACC Consensus Document on tilt-table testing (Benditt 1996). Other accepted HUT protocols do exist. Overnight fast, morning test ECG (at least 3 leads) Continuous blood pressure monitoring Patient remains supine on the table for 15-30 minutes. Tilt to 60-80 degrees for 20-45 minutes. Lower to horizontal and administer isoproterenol at 1-5 g/min until heart rate increases 25%. Re-tilt for 10 minutes� REFERENCE: Benditt DG, Ferguson DW, Grubb BP, et al. Tilt table testing for syncope. ACC Expert Consensus Document. JACC. 1996;28(1):263-275.
Presenter
Presentation Notes
So the Tilt is only as good as your history and physical, or your pretest probability. You will see that if your pretest probability is low and you have a negative tilt then your post test probability is of course low. However if your pretest probability is low and your tilt is positive then your post test probability is still low leaving you with a high chance of a false positive result. Vice versa, if you believe that the test will be positive and the test is positive then the post test probability is high. However if you have a strong suspicion of a positive test and have a negative tilt, then the post test probability is still high.
Tilt-Table Findings
NeurocardiogenicSudden hypotension with or without bradycardia
DysautonomicGradual parallel decline in systolic and diastolic blood pressure
POTSAn excessive heart rate response to maintain a low normal BP
Cerebral syncopeSyncope associated with cerebral vasoconstriction in the absence of systemic hypotension
PsychogenicNo change in heat rate, BP, EEG, transcranial blood flow
“Neurocardiogenic” Responses
Vasovagal International Study Group Type 1-Mixed: BP falls then HR (<3 sec pause) Type 2A - Cardioinhibitory: BP falls then HR Type 2B - Cardioinhibitory: HR falls >10 sec or >3
sec pause before BP falls Type 3 - Pure vasodepressor: BP falls
What does it all mean? Is it reproducible? How do we treat it?
Vasovagal International Study Group
Presenter
Presentation Notes
I believe an ILR or implantable loop recorder can be a complementary or stand alone diagnostic tool to help guide therapy.
ILR
Small subcutaneous implantable monitoring device
2009 ESC Guidelines recommend for: Early phase evaluation
Recurrent syncope with absence of high risk features Suspected or proven reflex syncope before pacing
Late evaluation High risk syncope without eitology after exhaustive w/u
Insertable Cardiac Monitors (ICM)
Reveal® System, Medtronic Inc.Minneapolis, MN-manual/auto trigger-remote download (CareLink®)
Confirm®, St Jude MedicalSt Paul, MN-manual/auto trigger-remote download (Merlin®)
Clinical Trials
• RAST (Randomized Assessment of Syncope Trial)1
• EasyAs 1 (Eastbourne Syncope Assessment Study)2
• ISSUE 1 (International Study on Syncope of3,4,5 Unexplained Etiology)
• ISSUE 2 and ISSUE 36,7
• PICTURE81 Krahn AD, et al. Circ. 2001;104:46-51.
1Krahn AD, et al. JACC 2003;42:495-501.2Farwell D et al. Eur Heart J 2006; 27: 351-356
3Moya A. Circulation 2001; 104: 1261-12674Menozzi C. Circulation 2002; 105: 2741-27455Brignole M. Circulation 2001; 104: 2045-2050
6Brignole M et al, Eur Heart J 2006; 27:10857Brignole M, Circulation 2012;125:2566-71
8Edvardsson N et al, Europace 2011;13:2629Hong PS et al, PACE 2010; 33;763-5
Randomized Assessment of Syncope Trial (RAST)
Results: Combining primary strategy with crossover, the diagnostic yield is
43% ILR only vs. 20% conventional only1
Cost/diagnosis is 26% less than conventional testing2
1Krahn AD, et al. Circ. 2001;104:46-51. 2Krahn AD, et al. JACC 2003;42:495-501.
Unexplained SyncopeEF > 35%
60 Patients
AECG, Tilt,EP Study
Diagnosis
ILR
+–
+
–
ILR Conventional Testing(AECG, Tilt, EPS)
30 Patients 30 Patients
PrimaryStrategy
Crossover
14 6
1 8+ +
Presenter
Presentation Notes
Dr. Andrew Krahn and his team at the University of Western Ontario authored the Randomized Assessment of Syncope Trial (RAST) in 20011 then followed up with a cost analysis of the same study in 2003.2 Prospective, randomized trial 60 patients with unexplained syncope after history, physical exam, ECG, and Holter monitor. EF > 35% (lower risk) 2 testing strategies: conventional, using an exterior loop recorder (ELR) or Holter, tilt test, �and electrophysiology study, or prolonged ILR monitoring. If patients remained undiagnosed after their assigned strategy, they were offered crossover to the alternate strategy. Overall, prolonged monitoring was more likely to result in a diagnosis than conventional testing, 43% vs. 20%, p=0.026. Subsequent cost studies showed a 26% reduction in cost per diagnosis ($2,016) with a strategy of primary monitoring (p=0.002). Prior to this study, the ILR was generally used as a last resort after other evaluation.� 1 Krahn AD, et al. Randomized Assessment of Syncope Trial: Conventional diagnostic testing versus a prolonged monitoring strategy. Circulation. 2001:104(1):46-51. 2 Krahn AD, et al. Cost implications of testing strategy in patients with syncope (RAST). JACC 2003;42:495-501.
Neurocardiogenic Syncope Tilt +, High suspicion (pretest probability
despite tilt -) Patient education about pathophysiology of
VVS and benign prognosis Increase salt and water intake If prodrome, sit or lie down Tilt-training or counterpressure manuevers Leg compression
Tilt training: > 90% effective1-3
First line: Treatment Options
1. Di Girolamo E Circulation 1999;100:17982. Reybrouck T PACE 2000;23:4933. Ector H et al PACE 1998; 21:193-6.
Tilt-Training: Clinical Outcomes
Of 42 tilt positive patients (21±13 min), home training: two 30 minute sessions daily
Outcome: 41/42 ->45 min asymptomatic tilt Follow-up: 15.1±7.8 mos
36 syncope free; 4 “presyncope”; 1 recurrence
Reybrouck et al. PACE 2000; 23:493-8
Neurocardiogenic Syncope
Presenter
Presentation Notes
The use of tilt-training has added an important dimension to treatment of recurrent VVS, and may also be of value in some forms of orthostatic hypotension. ADDITIONAL REFERENCES: .Ector H, Reybrouck T, Heidbuchel H, Gewillig M, Van de Werf F. Tilt training: a new treatment for recurrent neurocardiogenic syncope or severe orthostatic intolerance. PACE 1998;21:193-196. .Di Girolamo E, Di Iorio C, Leonzio L, Sabatini P, Barsotti A. Usefulness of a tilt training program for prevention of refractory neurocardiogenic syncope in adolescents. A controlled study. Circulation 1999;100: 1798-1801.
Neurocardiogenic Syncope
Beta-blockers SSRIs Midodrine Fludrocortisone
Anticholinergics (disopyramide, scopolamine)
Desmopressin Erythropoietin Theophylline
Drug Therapies: Second Line
Presenter
Presentation Notes
Pharmacologic therapy is second line and none with statistical evidence of their efficacy.
Beta Blockers
Initial observations suggest syncope reduction Rationale is that B-receptor involvement in
ventricular baroreceptor reflexes Isuprel (B agonist) can trigger hypotension and
bradycardia and BB can prevent the Isuprel effect
At least 4 randomized trials have failed to show benefit but difficult to demonstrate statistical benefit when placebo effect is so high
Best data from the POST trial
Presenter
Presentation Notes
The historical rationale for considering betablockers included animal studies demonstrating beta-receptor involvement in ventricular baroreceptor reflexes, the ability of isoproterenol to trigger hypotension and bradycardia during tilt testing 22, 23 , and the ability of beta-blockers to prevent the isoproterenol effect 24
208 patients with recurrent syncope and an abnormal tilt table test
Placebo vs metoprolol (avg dose 122mg daily) with 1 year follow up
Recurrent syncope occurred in 36 percent of both groups.
Withdrawal rates were 22 percent in both groups. Prespecified analyses according to age (categorized as
<42 versus ≥42 years) and tilt table test results did not identify any subgroups that benefited with metoprolol.
Sheldon R et al. Circulation 2006;113:1164-1170
Presenter
Presentation Notes
Figure 3. Top, Probability of remaining free of syncope or study discontinuation in an on-treatment analysis according to whether an isoproterenol infusion was required to provoke a positive tilt-test response. There was no significant difference in outcome in a subjects who had a positive isoproterenol tilt test (P=0.84), nor was there a significant difference in outcomes in subjects who had a positive drug-free tilt test (P=0.69). Bottom, Probability of remaining free of syncope in an on-treatment analysis according to whether the patients were <42 years old or ≥42 years old. There was no significant difference in outcome in subjects <42 years (P=0.52), nor was there a significant difference in outcomes in subjects ≥42 years old (P=0.30). The historical rationale for considering betablockers included animal studies demonstrating beta-receptor involvement in ventricular baroreceptor reflexes, the ability of isoproterenol to trigger hypotension and bradycardia during tilt testing 22, 23 , and the ability of beta-blockers to prevent the isoproterenol effect 24
FLUDROCORTISONE
Corticosteroid with primarily mineralcorticoid activity
Sodium and water retention and potassium excretion
POST II (multinational, randomized, controlled) 211 pts (fludrocortisone vs placebo) for 1yr Trend of less events in the fludrocortisone
group but NO statistical difference
MIDODRINE
Pro-drug- active metabolite is a peripheral alpha-1 adrenergic receptor Causes venoconstriction and arteriolar constriction Increases cardiac output and incresases peripheral
resistance
More effective than Na/volume therapy alone Challenge is frequent dosing compliance POST 4 (placebo vs midodrine) results due in
2017
Presenter
Presentation Notes
No rigorous data although it has tested well vs fluid and Na
SSRIs
High serotonin levels in the nervous system Serotonin modulates the CNS BP and HR Di Gerolamo et al conducted a randomized,
double-blind, placebo-controlled trial Paroxetine (20mg QD) vs placebo over ~25 mo Reduction in syncope recurrence
18% with Paxil vs 53% with placebo Other studies have found other SSRIs of no benefit Can be helpful in psychosocial stressors due to
syncope
Presenter
Presentation Notes
Higher serotonin levels in the nervous system therefore should be helpful
Pacemakers
Any role? Often a significant bradycardic response in VVS But severe vasodepressor reactions often coexist
Presenter
Presentation Notes
I am an EP, we have to implant something
Does Asystole Cause Syncope?
Asystole
Passed outTilt
Presenter
Presentation Notes
As mentioned before, sometimes the vasodepressor response occurs first and is the main culprit.
VPS-IVasovagal Pacemaker Study I
Connolly S, et al. J Am Coll Cardiol 1999; 33: 16-20.
Study Design:54 patients randomized, prospective, single center
_ 27 DDD pacemaker with rate drop response (RDR)_ 27 no pacemaker
Patient Inclusion Criteria:6 syncopal events ever+HUTRelative bradycardia*
Presenter
Presentation Notes
This was genious, do an invasive procedure that is supposed to cure vs do nothing and know that you were randomized to the do nothing group.
Risk of Syncope Recurrence100
908070605040
30201000 3 6 9 12 15
Time in Months
No Pacemaker
2P=0.000022
PacemakerCum
ulat
ive
Risk
(%)
Control Group n = 27 9 4 2 1 0Pacemaker Group n = 27 21 17 12 11 8
The VPS I Study
Connolly SJ. J Am Coll Cardiol 33:16-20, 1999
Inclusion: vasodepressor response
Presenter
Presentation Notes
54 patients were enrolled in the prospective North American Vasovagal Syncope trial. Patients were randomized to Rate Drop Response feature or to current therapy. Final analysis found: 6 / 27 with pacemakers had syncope recurrence 19 / 27 without pacemakers had syncope recurrence The study reported a 84% relative risk reduction in pacemaker group versus standard therapy. The study was halted when early stopping criteria were achieved (p<0.001 in favor of pacing).
VPS II Trial – Big Placebo Effect
Connolly S. JAMA 2003:289:2224–2229
Time to First Recurrence of Syncope
•Syncope > 5 total or > 2 episodes in 2 years, positive tilt, age > 19
•RR reduction 29%
Presenter
Presentation Notes
Lets repeat the study but now put PMs in both groups…Oops! No difference. A meta-analysis of nine randomized trials (two double blind and seven open label or single blind; total n = 430) of permanent pacemaker therapy for vasovagal syncope showed no overall benefit from pacemaker implantation and suggested that in the unblinded trials, an "expectation effect" led to an overestimation of the benefits of pacing [42]. Both double blind trials included in the meta-analysis (VPS II and SYNPACE) showed no statistically significant improvement with pacing [43,44].
ILR FIRST THEN PM???• ISSUE 3 Population• Diagnosis: Reflex (neurally-mediated) VVS• Mean age at presentation: >60 years• Recurrent syncope beginning in middle or older age • Clinical presentation sufficiently severe to require
treatment (high risk and/or high frequency)• Atypical presentation without warning• Injuries related to presentation without warning• ILR documentation of marked bradycardia (mean pause
duration, 11 seconds)Brignole M, Circulation 2012;125:2566-71
ISSUE-3 Study design
-mediated syncope
ILR implantation (Reveal DX/XT)
ILR follow-up (max 2 yrs)
ILR screening phaseILR eligibility criteria:• Asystolic syncope ≥3 s, or• Non-syncopal asystole ≥6 s
ISSUE 3 studyphase
Randomization
PM ON PM OFF
Time to first syncope recurrenceEndpointBrignole M, Circulation 2012;125:2566-71
Presenter
Presentation Notes
However in contrast, ILR data can help guide therapy. 77 patients who had VVS with ILR implant with demonstration of asystolic syncope of >3 sec or non-syncopal asytole >6 s
0
.1
.2
.3
.4
.5
.6
.7
.8
.9
1
Free
dom
from
syn
copa
l rec
urre
nce
38 32 27 22 16 14 13 13 11Pm ON39 31 25 21 21 18 15 12 8Pm OFF
Number at risk
0 3 6 9 12 15 18 21 24Months
Kaplan-Meier survival estimates
log rank: p=0.039RRR at 2 yrs: 57%
PM ON
PM OFF
ISSUE-3: Intention-to-Treat
25%
37%
25%
57%
Brignole M, Circulation 2012;125:2566-71
Presenter
Presentation Notes
A possible reason for the difference in results between the ISSUE-3 trial and earlier double-blind trials is that the ISSUE-3 trial used ILR to identify candidates for pacing in contrast to use of tilt testing as a criterion in earlier trials. As noted above, ILR may more accurately identify a causative relationship between bradyarrhythmias and syncope than tilt table testing or adenosine administration.
ISSUE-3 Conclusion
• In patients ≥40 years with severe asystolic NMS:
•Dual-chamber pacing reduces recurrence of syncope
•The 32% absolute and 57% relative syncope reduction rate support use pacing.
• The strategy of using ILR to determine indication for pacing likely explains the positive outcome and difference from prior negative results in pacemaker studies.
Brignole M, Circulation 2012;125:2566-71
Carotid Sinus Syndrome (CSS)
Syncope clearly associated with carotid sinus stimulation is rare (≤1% of syncope)
CSS may be an important cause of unexplained syncope / falls in older individuals
Brignole et al. Eur Heart J 2001;22:1256--1306
Presenter
Presentation Notes
Carotid sinus syndrome (CSS) is an important and often overlooked cause of syncope, and in addition is believed to be a frequent cause of unexplained falls in older individuals. The method of carotid sinus massage, and the findings diagnostic of CSS were presented on previous slides REFERENCE Brignole M, Alboni P, Benditt DG, et al. Guidelines on management (diagnosis and treatment) of syncope. Eur Heart Journal 2001; 22: 1256-1306.
CSSProposed Mechanisms
• Sensory nerve endings in the carotid sinus walls respond to deformation
• “Deafferentation” of neck muscles may contribute as the CNS doesn’t realize the neck is moving
• Afferent signals to brain stem interpreted as arterial pressure
• Reflex increase in efferent vagal activity and diminution of sympathetic tone results in bradycardia and vasodilation
Carotid Sinus
Presenter
Presentation Notes
Etiology of CSS The etiology of CSS rests in part from afferent signals arising in the carotid baroreceptors, and inappropriate concomitant signals from nearby neck muscles: Sensory nerve endings in the carotid sinus walls respond to deformation. An increase in afferent traffic results in cardioinhibition and vasodilatation. Deafferentation of nearby neck muscles may contribute. The CNS is not informed of neck movement and consequently the carotid baroreceptor afferents are interpreted as indicating a rise in central arterial pressure. ____________________ Blanc JJ, L’Heveder J, Mansourati J, et al. Pathophysiology of carotid sinus syndrome. In: Neurally mediated syncope: Pathophysiology, investigation and treatment. Blanc JJ, Benditt D, Sutton R (eds). Armonk, NY: Futura, 1996, pp. 25-29. Kenny RA, McIntosh SJ. Carotid sinus syndrome. In: Syncope in the older patient. Kenny RA (ed). London: Chapman & Hall Medical, 1996, pp. 107-108.
CSS - Carotid Sinus SyndromeDiagnosis
• Carotid Sinus Hypersensitivity (CSH) implies positive response to carotid massage: ≥50 mmHg drop in systolic pressure ≥6 sec asystolic pause CSS = CSH + Reproduction of symptoms
• CSH without symptoms is not treated• CSS needs a DDD PM
Moya A et al, ESC Syncope Guidelines, Eur Heart J 2009; 30: 2631-71
Presenter
Presentation Notes
Carotid sinus syndrome (CSS) is an important and often overlooked cause of syncope, and in addition is believed to be a frequent cause of unexplained falls in older individuals. The method of carotid sinus massage, and the findings diagnostic of CSS were presented on previous slides Brignole M, Alboni P, Benditt DG, et al. Guidelines on management (diagnosis and treatment) of syncope. Eur Heart Journal 2001; 22: 1256-1306. Underlying Cause: Carotid Sinus Hypersensitivity (CSH) The underlying cause of CSS is considered to be a hypersensitive carotid sinus. Carotid Sinus Hypersensitivity (CSH) is diagnosed by using Carotid Sinus Massage (CSM). CSH is considered present when a 5-second massage results in either more than 3 seconds of asystole or more than a 50 mm/Hg fall in systolic blood pressure. CSH is a necessary but not a sufficient condition for diagnosing CSS. The latter refers to symptoms such as bradycardia, dizziness, pre-syncope, syncope, and falling resulting from a hypersensitive carotid sinus reflex (Katritsis 1991). Many subjects who exhibit CSH are free of symptoms and require no treatment. In one study, 38% of patients being catheterized for angiography responded positively to CSM (Brown 1980). _________________ Brown KA, Maloney JD, Smith HC, et al. Carotid sinus reflex in patients undergoing coronary angiography: Relationship of degree and location of coronary artery disease to response to carotid sinus massage. Circulation. 1980; 62:697-703. Katritsis D, Ward DE, Camm AJ. Can we treat carotid sinus syndrome? PACE. 1991;14(9):1367-74. Sutton R. Carotid sinus syndrome: clinical presentation, epidemiology, and natural history. In: Neurally mediated syncope: Pathophysiology, investigation and treatment. Blanc JJ, Benditt D, Sutton R (eds). Armonk, NY: Futura, 1996, p. 138.
Conclusion
Syncope is common Risk stratification important High risk patients require further testing and
hospitalization Low risk patients can be discharged for further
evaluation as an outpatient
Etiology can be difficult to decipher Requires good history and physical Treatment is education first Remember that placebo has been very effective
thus education and empowerment should be as effective
Tilt studies and ILR monitoring can be helpful PMs for >3s asystolic syncope, asymptomatic >6s
pause and Carotid Sinus Syndrome
Questions?
