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Slide 1-

Syncope A Diagnostic and Treatment Strategy David G. Benditt, M.D. University of Minnesota Medical School Minneapolis, MN USA Richard Sutton, DScMed Royal Brompton Hospital London, UK
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Transient Loss of Consciousness (TLOC)
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Classification of Transient Loss of Consciousness (TLOC) Syncope Neurally-mediated reflex syndromes Orthostatic hypotension Cardiac arrhythmias Structural cardiovascular disease Disorders Mimicking Syncope With loss of consciousness, i.e., seizure disorders, concussion Without loss of consciousness, i.e., psychogenic “pseudo-syncope” Real or Apparent TLOC Brignole M, et al. Europace, 2004;6:467-537.
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Syncope – A Symptom, Not a Diagnosis Self-limited loss of consciousness and postural tone Relatively rapid onset Variable warning symptoms Spontaneous, complete, and usually prompt recovery without medical or surgical intervention Underlying mechanism is transient global cerebral hypoperfusion. Brignole M, et al. Europace, 2004;6:467-537.
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Presentation Overview I. Etiology, Prevalence, Impact II. Diagnosis III. Specific Conditions and Treatment IV. Special Issues
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Section I: Etiology, Prevalence, Impact
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Causes of True Syncope Orthostatic Cardiac Arrhythmia Structural Cardio- Pulmonary 1 VVS CSS • Situational Cough Post- Micturition 2 Drug-Induced • ANS Failure Primary Secondary 3 Brady SN Dysfunction AV Block • Tachy VT SVT Long QT Syndrome 4 Acute Myocardial Ischemia Aortic Stenosis HCM Pulmonary Hypertension Aortic Dissection Neurally- Mediated Unexplained Causes = Approximately 1/3 DG Benditt, MD. U of M Cardiac Arrhythmia Center
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Syncope Mimics Acute intoxication (e.g., alcohol) Seizures Sleep disorders Somatization disorder (psychogenic pseudo-syncope) Trauma/concussion Hypoglycemia Hyperventilation Brignole M, et al. Europace, 2004;6:467-537.
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Impact of Syncope 1Kenny RA, Kapoor WN. In: Benditt D, et al. eds. The Evaluation and Treatment of Syncope. Futura;2003:23-27. 2Kapoor W. Medicine. 1990;69:160-175. 3Brignole M, et al. Europace. 2003;5:293-298. 4 Blanc J-J, et al. Eur Heart J. 2002;23:815-820. 5Campbell A, et al. Age and Ageing. 1981;10:264-270. 40% will experience syncope at least once in a lifetime1 1-6% of hospital admissions2 1% of emergency room visits per year3,4 10% of falls by elderly are due to syncope5 Major morbidity reported in 6%1 eg, fractures, motor vehicle accidents Minor injury in 29%1 eg, lacerations, bruises
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Impact of Syncope: US Trends *All patients discharged with syncope and collapse (ICD-9 Code:780.2) listed among diagnoses. NHDS 2003. NAMCS 2002. Inpatient Trend* Physician Office Visits** **Syncope and collapse (ICD-9 Code: 780.2) listed as primary reason for visit. (000s) (000s)
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Impact of Syncope: US Trends Emergency Department Visits* Hospital Outpatient Visits* (000s) + Not available NHAMCS 2002. + *Syncope and collapse (ICD-9 Code:780.2) listed as primary reason for visit. (000s)
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Impact of Syncope: NHS Hospitals, England, 2002-2003* 74,813 hospital consults for syncope and collapse 80% required hospital admission Average length of stay: 6.1 days 327,201 hospital bed days, second only to senility *Hospital Episode Statistics, Dept. of Health, Eng. 2002-2003.
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Impact of Syncope: Costs Estimated hospital costs exceeded $10 billion US1 Estimated physician office expenses exceeded $470 million2 £104,285 spent on 1,334 patients with syncopal codes (UK) (EaSyAS)3 Hospital admission: 67% of investigational costs Over $7 billion is spent annually in the US to treat falls in older adults4 1Kenny RA, Kapoor WN. In: Benditt D, et al. eds. The Evaluation and Treatment of Syncope. Futura;2003:23-27. 2OutPatientView v. 6.0. Solucient LLC, Evanston IL. 3Farwell D, et al. J Cardiovasc Electrophysiol. 2002;13(Supp):S9-S13. 4Olshansky B. In: Grubb B and Olshansky B. eds. Syncope: Mechanisms and Management. Futura. 1998:15-71.
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Impact of Syncope: Quality of Life 1Linzer M. J Clin Epidemiol. 1991;44:1037. 2Linzer M. J Gen Int Med. 1994;9:181. Anxiety/ Depression Alter Daily Activities Restricted Driving Change Employment 73%1 71%2 60%2 37%2 Percent of Patients
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Quality of Life: UK Population Norms vs. Syncope Patients Rose M, et al. J Clin Epidemiol. 2000;53:1209-1216. 3% 26% 4% 37% 1% 9% 36% 49% 19% 43% Mobility Usual Activities Self-Care Pain/ Discomfort Anxiety/ Depression % Prevalence
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Syncope Mortality Low mortality vs. high mortality Neurally-mediated syncope vs. syncope with a cardiac cause Soteriades ES, Evans JC, Larson MG, et al. Incidence and prognosis of syncope. N Engl J Med. 2002;347(12):878-885. [Framingham Study Population]
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Implications of Syncope for Driving a Vehicle Those who drive and have recurrent syncope risk their lives and the lives of others Places considerable burden on the physician Essential to know local laws and physician responsibilities Some states – Invasion of privacy to notify motor vehicle department* Other states – Reporting is mandatory* If the patient has sufficient warning of impending syncope – Driving may be permitted Olshansky B, Grubb B. In: Syncope: Mechanisms and Management. Futura. Armonk, NY. 1998. *Medtronic, Inc. Follow-up Forum. 1995/96;1(3):8-10.
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Challenges of Syncope Diagnosis Complex Quality of life implications Work Mobility (automobiles) Psychological Cost Cost/year Cost/diagnosis
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Section II: Diagnosis
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Diagnostic Objectives Distinguish true syncope from syncope mimics Determine presence of heart disease Establish the cause of syncope with sufficient certainty to: Assess prognosis confidently Initiate effective preventive treatment
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A Diagnostic Plan is Essential Initial Examination Detailed patient history Physical exam ECG Supine and upright blood pressure Monitoring Holter Event Insertable Loop Recorder (ILR) Cardiac Imaging Special Investigations Head-up tilt test Hemodynamics Electrophysiology study Brignole M, et al. Europace, 2004;6:467-537.
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Diagnostic Flow Diagram for TLOC Brignole M, et al. Europace, 2004;6:467-537.
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Initial Exam: Detailed Patient History Circumstances of recent event Eyewitness account of event Symptoms at onset of event Sequelae Medications Circumstances of more remote events Concomitant disease, especially cardiac Pertinent family history Cardiac disease Sudden death Metabolic disorders Past medical history Neurological history Syncope Brignole M, et al. Europace, 2004;6:467-537.
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Initial Exam: Thorough Physical Vital signs Heart rate Orthostatic blood pressure change Cardiovascular exam: Is heart disease present? ECG: Long QT, pre-excitation, conduction system disease Echo: LV function, valve status, HCM Neurological exam Carotid sinus massage Perform under clinically appropriate conditions preferably during head-up tilt test Monitor both ECG and BP Brignole M, et al. Europace, 2004;6:467-537.
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Carotid Sinus Massage (CSM) Method1 Massage, 5-10 seconds Don’t occlude Supine and upright posture (on tilt table) Outcome 3 second asystole and/or 50 mmHg fall in systolic BP with reproduction of symptoms = Carotid Sinus Syndrome Absolute contraindications2 Carotid bruit, known significant carotid arterial disease, previous CVA, MI last 3 months Complications Primarily neurological Less than 0.2%3 Usually transient 1Kenny RA. Heart. 2000;83:564. 2Linzer M. Ann Intern Med. 1997;126:989. 3Munro N, et al. J Am Geriatr Soc. 1994;42:1248-1251.
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Other Diagnostic Tests Ambulatory ECG Holter monitoring Event recorder Intermittent vs. Loop Insertable Loop Recorder (ILR) Head-Up Tilt (HUT) Includes drug provocation (NTG, isoproterenol) Carotid Sinus Massage (CSM) Adenosine Triphosphate Test (ATP) Electrophysiology Study (EPS) Brignole M, et al. Europace, 2004;6:467-537.
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Heart Monitoring Options ILR Event Recorders (non-lead and loop) Holter Monitor 12-Lead 2 Days 7-30 Days Up to 14 Months 10 Seconds OPTION TIME (Months) 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 Brignole M, et al. Europace, 2004;6:467-537.
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Diagnostic Assessment: Yields (N=3411 to 4332) References Available
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Neurological Tests: Rarely Diagnostic for Syncope EEG, Head CT, Head MRI May help diagnose seizure Brignole M, et al. Europace. 2004;6:467-537.
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Head-Up Tilt Test (HUT) Protocols vary Useful as diagnostic adjunct in atypical syncope cases Useful in teaching patients to recognize prodromal symptoms Not useful in assessing treatment Brignole M, et al. Europace. 2004;6:467-537.
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Head-up Tilt Test Carlos Morillo, MD, FRCPC Professor, Faculty of Health Sciences McMaster University, Hamilton Ontario Click once on image to play video.
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Head-Up Tilt Test: ECG Leads and Intra-Arterial Pressure Tracing DG Benditt, MD. U of M Cardiac Arrhythmia Center 2 1
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Adenosine Triphosphate (ATP) Test Ongoing investigation in the US Provokes a short and potent cardioinhibitory vasovagal response Advantages Simple Inexpensive Correlation with pacing benefit Seems to identify a unique mechanism of syncope found in patients with: Advanced age More hypertension More ECG abnormalities Brignole M. Heart. 2000;83:24-28. Donateo P. J Am Coll Cardiol. 2003;41:93-98. Flammang D. Circ. 1999;99:2427-2433.
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Reveal® Plus ILR Insertable Loop Recorder (ILR) Typical Location of the Reveal® Plus ILR Click once on black screen to play video.
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Insertable Loop Recorder (ILR) The ILR is an implantable patient – and automatically – activated monitoring system that records subcutaneous ECG and is indicated for: Patients with clinical syndromes or situations at increased risk of cardiac arrhythmias Patients who experience transient symptoms that may suggest a cardiac arrhythmia
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Insertable Loop Recorder (ILR) Click once on black screen to play video.
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Symptom-Rhythm Correlation with the ILR CASE: 65 year-old man with syncope accompanied by brief retrograde amnesia. Medtronic data on file. CASE: 56 year-old woman with refractory syncope accompanied with seizures.
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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.
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Conventional EP Testing in Syncope Greater diagnostic value in older patients or those with SHD Less diagnostic value in healthy patients without SHD Useful diagnostic observations: Inducible monomorphic VT SNRT > 3000 ms or CSNRT > 600 ms Inducible SVT with hypotension HV interval ≥ 100 ms (especially in absence of inducible VT) Pacing induced infra-nodal block Benditt D. In: Topol E, ed. Textbook of Cardiovascular Medicine. Lippencott;2002:1529-1542. Lu F, et al. In: Benditt D, et al. The Evaluation and Treatment of Syncope. Futura. 2003;80-95. Brignole M, et al. Europace. 2004;6:467-537.
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Diagnostic Limitations of EPS Difficult to correlate spontaneous events and laboratory findings Positive findings1 Without SHD: 6-17% With SHD: 25-71% Less effective in assessing bradyarrhythmias than tachyarrhythmias2 EPS findings must be consistent with clinical history Beware of false positive 1Linzer M, et al. Ann Int Med. 1997;127:76-86. 2Lu F, et al. In: Benditt D, et al. The Evaluation and Treatment of Syncope. Futura. 2003;80-95.
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ISSUE International Study of Syncope of Uncertain Etiology Multicenter, international, prospective study Analyzed the diagnostic contribution of an ILR in three predefined groups of patients with syncope of uncertain origin: Isolated syncope: No SHD, Normal ECG1 Negative tilt Positive tilt Patients with heart disease and negative EP test2 Patients with bundle branch block and negative EP test3 1Moya A. Circulation. 2001; 104:1261-1267. 2Menozzi C, et al. Circulation. 2002;105:2741-2745. 3Brignole M, et al. Circulation. 2001;104:2045-2050.
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ISSUE Patients with Isolated Syncope and Tilt-Positive Syncope Moya A. Circulation. 2001;104:1261-1267.
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ISSUE Isolated Syncope vs. Tilt-Positive Syncope Conclusions Results similar in the two arms, including syncope recurrence and ECG correlation Tilt-negative patients had as many bradycardias (18%) as tilt-positive patients (21%) Most frequent finding was asystole secondary to progressive sinus bradycardia, suggesting a neuro-mediated origin Homogeneous findings from tilt-negative and tilt-positive infer low sensitivity of tilt-testing Moya A. Circulation. 2001;104:1261-1267.
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ISSUE Patients with Heart Disease and a Negative EP Test Menozzi C, et al. Circulation. 2002;105:2741-2745. AV block + asystole: 1 A.Fib + asystole: 1 Sinus arrest: 1 Sinus tachycardia: 1 Rapid A.Fib: 2 Sustained VT: 1 Parox. A.Fib/AT: 1 Post tachycardia pause: 1 No rhythm variations: 4 Sinus tachycardia: 1
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ISSUE Patients with Heart Disease and a Negative EP Test Conclusions Patients with unexplained syncope, overt heart disease, and negative EP study had a favorable medium-term outcome Mechanism of syncope was heterogeneous Ventricular tachyarrhythmia was unlikely “ILR-guided strategy seems reasonable, with specific therapy safely delayed until a definite diagnosis is made.” Menozzi C, et al. Circulation. 2002;105:2741-2745.
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ISSUE Patients with Bundle Branch Block and Negative EP Test Brignole M., ET AL.,Circulation. 2001;104:2045-2050. * 5 of these also had ≥1 presyncope ** Drop-out before primary-end point ILR-Detected: 19 AVB: 12 (63%) SA: 4 (21%) Asystole-undefined: 1 (5%) NSR: 1 (5%) Sinus tachy: 1 (5%) Not Detected: 3 ILR-Detected Pre-Syncope: 2 Pts (4%)** AVB: 2 (4%)
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ISSUE Patients with Bundle Branch Block and Negative EP Test Conclusion: In patients with BBB and negative EP study, most syncopal recurrences have a homogeneous mechanism that is characterized by prolonged asystolic pauses mainly attributable to sudden-onset paroxysmal AV block Brignole M. Circulation. 2001;104:2045-2050.
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Section III: Specific Conditions and Treatment
Slide 49-

Specific Conditions Cardiac arrhythmia Brady/Tachy Long QT syndrome Torsade de pointes Brugada Drug-induced Structural cardio-pulmonary Neurally-mediated Vasovagal Syncope (VVS) Carotid Sinus Syndrome (CSS) Orthostatic
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Cardiac Syncope Includes cardiac arrhythmias and SHD Often life-threatening May be warning of critical CV disease Tachy and brady arrhythmias Myocardial ischemia, aortic stenosis, pulmonary hypertension, aortic dissection Assess culprit arrhythmia or structural abnormality aggressively Initiate treatment promptly Brignole M, et al. Europace. 2004;6:467-537.
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“…cardiac syncope can be a harbinger of sudden death.” Survival with and without syncope 6-month mortality rate of greater than 10% Cardiac syncope doubled the risk of death Includes cardiac arrhythmias and SHD Soteriades ES, et al. N Engl J Med. 2002;347:878.
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Syncope Due to Structural Cardiovascular Disease: Principle Mechanisms Acute MI/Ischemia 2° neural reflex bradycardia – Vasodilatation, arrhythmias, low output (rare) Hypertrophic cardiomyopathy Limited output during exertion (increased obstruction, greater demand), arrhythmias, neural reflex Acute aortic dissection Neural reflex mechanism, pericardial tamponade Pulmonary embolus/ pulmonary hypertension Neural reflex, inadequate flow with exertion Valvular abnormalities Aortic stenosis – Limited output, neural reflex dilation in periphery Mitral stenosis, atrial myxoma – Obstruction to adequate flow Brignole M, et al. Europace. 2004;6:467-537.
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Syncope Due to Cardiac Arrhythmias Bradyarrhythmias Sinus arrest, exit block High grade or acute complete AV block Can be accompanied by vasodilatation (VVS, CSS) Tachyarrhythmias Atrial fibrillation/flutter with rapid ventricular rate (eg, pre-excitation syndrome) Paroxysmal SVT or VT Torsade de pointes Brignole M, et al. Europace. 2004;6:467-537.
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ILR Recordings CASE: 28 year-old man presents to ER multiple times after falls resulting in trauma. VT: Ablated and medicated. CASE: 83 year-old woman with syncope due to bradycardia: Pacemaker implanted. Reveal ® ILR recordings; Medtronic data on file.
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Cardiac Rhythms During Unexplained Syncope Seidl K. Europace. 2000;2(3):256-262. Krahn AD. PACE. 2002;25:37-41. Medtronic ILR Replacement Data. FY03, 04. On file. No Recurrence 36% (31-48%) Normal Sinus Rhythm 31% (17-44%) Other 11% Arrhythmia 22% (13-32%) Tachycardia 6% (2-11%) Bradycardia 16% (11-21%) Composite: N=133 to 7109
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Long QT Syndromes Mechanism Abnormalities of sodium and/or potassium channels Susceptibility to polymorphic VT (Torsade de pointes) Prevalence Drug-induced forms – Common Genetic forms – Relatively rare, but increasingly being recognized “Concealed” forms: May be common Provide basis for drug-induced torsade Schwartz P, Priori S. In: Zipes D and Jalife J, eds. Cardiac Electrophysiology. Saunders;2004:651-659.
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Syncope: Torsade de Pointes From the files of DG Benditt, MD. U of M Cardiac Arrhythmia Center
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Long QT Syndromes: 12-Lead ECG From the files of DG Benditt, MD. U of M Cardiac Arrhythmia Center
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Drug-Induced QT Prolongation (List is continuously being updated) Antiarrhythmics Class IA ...Quinidine, Procainamide, Disopyramide Class III…Sotalol, Ibutilide, Dofetilide, Amiodarone, NAPA* Antianginal Agents Bepridil* Psychoactive Agents Phenothiazines, Amitriptyline, Imipramine, Ziprasidone Antibiotics Erythromycin, Pentamidine, Fluconazole, Ciprofloxacin and its relatives Nonsedating antihistamines Terfenadine*, Astemizole Others Cisapride*, Droperidol, Haloperidol *Removed from U.S. Market Brignole M, et al. Europace, 2004;6:467-537.
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Treatment of Long QT Suspicion and recognition are critical Emergency treatment Intravenous magnesium Pacing to overcome bradycardia or pauses Isoproterenol to increase heart rate and shorten repolarization ICD if prior SCA or strong family history If drug induced: Reverse bradycardia Withdraw drug Avoid ALL long-QT provoking agents If genetic: Avoid ALL long-QT provoking agents For more information visit www.longqt.org Schwartz P, Priori S. In: Zipes D and Jalife J, eds. Cardiac Electrophysiology. Saunders;2004:651-659.
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Treatment of Syncope Due to Bradyarrhythmia Class I indication for pacing using dual chamber system wherever possible Ventricular pacing in atrial fibrillation with slow ventricular response ACC/AHA/NASPE 2002 Guideline Update. Circ. 2002;106:2145-2161.
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Treatment of Syncope Due to Tachyarrhythmia Atrial tachyarrhythmias AVRT due to accessory pathway – Ablate pathway AVNRT – Ablate AV nodal slow pathway Atrial fib – Pacing, linear/focal ablation for paroxysmal AF Atrial flutter – Ablate the IVC-TV isthmus of the re-entrant circuit for ‘typical’ flutter Ventricular tachyarrhythmias Ventricular tachycardia – ICD or ablation where appropriate Torsade de pointes – Withdraw offending drug or implant ICD (long QT/Brugada/short QT) Drug therapy may be an alternative in many cases Brignole M, et al. Europace. 2004;6:467-537.
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Neurally-Mediated Reflex Syncope Vasovagal Syncope (VVS) Carotid Sinus Syndrome (CSS) Situational syncope Post-micturition Cough Swallow Defecation Blood drawing, etc. Brignole M, et al. Europace, 2004;6:467-537.
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Pathophysiology Autonomic Nervous System Benditt D, et al. Neurally mediated syncope: Pathophysiology, investigations and treatment. Blanc JJ, et al. eds. Futura. 1996.
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VVS Clinical Pathophysiology Neurally-mediated physiologic reflex mechanism with two components: 1. Cardioinhibitory (↓ HR) 2. Vasodepressor (↓ BP) despite heart beats, no significant BP generated Both components are usually present Wieling W, et al. In: Benditt D, et al. The Evaluation and Treatment of Syncope. Futura. 2003;11-22. 1 2
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VVS Incidence Most common form of syncope 8% to 37% (mean 18%) of syncope cases Depends on population sampled Young without SHD, ↑ incidence Older with SHD, ↓ incidence Linzer M, et al. Ann Intern Med. 1997;126:989.
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VVS vs. CSS In general: VVS patients younger than CSS patients Ages range from adolescence to older adults (median 43 years) Linzer M, et al. Ann Intern Med. 1997;126:989.
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VVS Recurrences 1Savage D, et al. STROKE. 1985;16:626-29. 2Sheldon R, et al. Circulation. 1996;93:973-81. 35% of patients report syncope recurrence during follow-up ≤3 years1 Positive HUT with >6 lifetime syncope episodes: recurrence risk >50% over 2 years2
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From the files of DG Benditt, MD. U of M Cardiac Arrhythmia Center VVS Spontaneous 16 year-old male, healthy, athletic, monitored for fainting.
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VVS Diagnosis History and physical exam, ECG and BP Head-Up Tilt (HUT) – Protocol: Fast > 2 hours ECG and continuous blood pressure, supine, and upright Tilt to 70°, 20 minutes Isoproterenol/Nitroglycerin if necessary End point – Loss of consciousness 60° - 80° Benditt D, et al. JACC. 1996;28:263-275. Brignole M, et al. Europace, 2004;6:467-537.
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VVS General Treatment Measures Optimal treatment strategies for VVS are a source of debate Treatment goals Acute intervention Physical maneuvers, eg, crossing legs or tugging arms Lowering head Lying down Long-term prevention Tilt training Education Diet, fluids, salt Support hose Drug therapy Pacing Brignole M, et al. Europace, 2004;6:467-537.
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VVS Tilt Training Protocol Objectives Enhance orthostatic tolerance Diminish excessive autonomic reflex activity Reduce syncope susceptibility/recurrences Technique Prescribed periods of upright posture against a wall Start with 3-5 min BID Increase by 5 min each week until a duration of 30 min is achieved Reybrouck T, et al. PACE. 2000;23(4 Pt. 1):493-498.
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VVS Tilt Training: Clinical Outcomes Treatment of recurrent VVS Reybrouck, et al.*: Long-term study 38 patients performed home tilt training After a period of regular tilt training, 82% remained free of syncope during the follow-up period However, at the 43-month follow-up, 29 patients had abandoned the therapy Conclusion: The abnormal autonomic reflex activity of VVS can be remedied. Compliance may be an issue. *Reybrouck T, et al. PACE. 2000;23:493-498.
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VVS Tilt Training: Clinical Outcomes Foglia-Manzillo, et al.*: Short-term study 68 patients 35 tilt training 33 no treatment (control) Tilt table test conducted after 3 weeks 19 (59%) of tilt trained and 18 (60%) of controls had a positive test Tilt training was not effective in reducing tilt testing positivity rate Poor compliance in the majority of patients with recurrent VVS *Foglio-Manzillo G, et al. Europace. 2004;6:199-204.
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VVS Pharmacologic Treatment Fludrocortisone Beta-adrenergic blockers Preponderance of clinical evidence suggests minimal benefit1 SSRI (Selective Serotonin Re-Uptake Inhibitor) 1 small controlled trial2 Vasoconstrictors 1 negative controlled trial (etilefrine)3 2 positive controlled trials (midodrine)4,5 1Brignole M, et al. Europace, 2004;6:467-537. 2Di Girolamo E, et al. JACC. 1999;33:1227-1230. 3Raviele A, et al. Circ. 1999;99:1452-1457. 4Ward C, et al. Heart. 1998;79:45-49. 5Perez-Lugones A, et al. J Cardiovasc Electrophysiol. 2001;12(8):935-938.
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Midodrine for VVS Perez-Lugones A, Schweikert R, Pavia S, et al. J Cardiovasc Electrophysiol. 2001;12(8):935-938. Months p < 0.001 Symptom-Free Interval 0 Fluid Midodrine
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The Role of Pacing as Therapy for Syncope VVS with +HUT and cardioinhibitory response: Class IIb indication for pacing Three randomized, prospective trials reported benefits of pacing in select VVS patients: VPS I1 VASIS2 SYDIT3 Subsequent study results less clear VPS II4 Synpace5 INVASY6 1Connolly SJ. J Am Coll Cardiol. 1999;33:16-20. 2Sutton R. Circulation. 2000;102:294-299. 3Ammirati F. Circ. 2001;104:52-57. 4Connolly S. JAMA. 2003;289:2224-2229. 5Giada F. PACE . 2003;26:1016 (abstract). 6Occhetta E, et al. Europace. 2004;6:538-547.
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VPS I (North American Vasovagal Pacemaker Study) Objective: To evaluate pacemaker therapy for severe recurrent vasovagal syncope Randomized, prospective, single center N=54 patients 27: DDD pacemaker with rate drop response 27: No pacemaker Inclusion: Vasodepressor response Primary outcome: First recurrence of syncope Connolly SJ. J Am Coll Cardiol. 1999;33:16-20.
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100 90 80 70 60 50 40 30 20 10 0 0 3 6 9 12 15 Time in Months No Pacemaker (PM) 2P=0.000022 Pacemaker Cumulative Risk (%) Connolly SJ. J Am Coll Cardiol. 1999;33:16-20. Results: 6 (22%) with PM had recurrence vs. 19 (70%) without PM 84% RRR (2p=0.000022) VPS I (North American Vasovagal Pacemaker Study)
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VASIS (VAsovagal Syncope International Study) Objective: To evaluate pacemaker therapy for severe cardioinhibitory tilt-positive neurally mediated syncope Randomized, prospective, multi-center N=42 patients 19: DDI pacemaker (80 bpm) with rate hysteresis (45 bpm) 23: No pacemaker Inclusion: Positive cardioinhibitory response Primary outcome: First recurrence of syncope Sutton R. Circulation. 2000;102:294-299.
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Sutton R. Circulation. 2000;102:294-299. Pacemaker (PM) No Pacemaker p=0.0004 Years % Syncope-Free 100 80 60 40 20 0 2 3 4 5 6 Results: 1 (5%) with PM had recurrence vs. 14 (61%) without PM VASIS (VAsovagal Syncope International Study)
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SYDIT (SYncope DIagnosis and Treatment) Objective: To compare the effects of cardiac pacing with pharmacological therapy in patients with recurrent vasovagal syncope Randomized, prospective, multi-center N=93 patients 46: DDD pacemaker with rate drop response 47: Atenolol 100 mg/d Inclusion: Positive HUT with relative bradycardia Primary outcome: First recurrence of syncope Ammirati F. Circulation. 2001;104:52-57.
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SYDIT (SYncope DIagnosis and Treatment) Ammirati F. Circulation. 2001;104:52-57. 0.6 0.7 0.8 0.9 1.0 0 100 200 300 400 500 600 700 800 900 1000 Drug Pacemaker (PM) Time (Days) % Syncope-Free p=0.0032 Results: 2 (4%) with PM had syncope recurrence vs. 12 (26%) without PM
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VPS II (Vasovagal Pacemaker Study II) Objective: To determine if pacing therapy reduces the risk of syncope in patients with vasovagal syncope Randomized, double-blind, prospective, multi-center N=100 patients 52: Only sensing without pacing 48: DDD pacemaker with rate drop response Inclusion: Positive HUT with (HRxBP) < 6000/min x mm Hg Primary outcome: First recurrence of syncope Connolly S. JAMA. 2003;289:2224-2229.
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Dual Chamber Pacing (DDD) Only Sensing Without Pacing (ODO) 1.0 0.8 0.6 0.4 0.2 0 Months Since Randomization Cumulative Risk 6 5 4 3 2 1 0 Connolly S. JAMA. 2003;289:2224–2229. Results: 33% with pacing had recurrence vs. 42% with only sensing (not statistically significant) VPS II (Vasovagal Pacemaker Study II)
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SYNPACE (Vasovagal SYNcope and PACing) Objective: To determine if pacing therapy will reduce syncope relapses in patients with recurrent vasovagal syncope, compared to those with a pacemaker programmed to OFF Randomized, double-blind, prospective, multi-center, placebo-controlled N=29 patients 16: DDD PM with rate drop response programmed ON 13: PM programmed OFF (OOO mode) Inclusion: Recurrent VVS and +HUT with asystolic or mixed response Primary outcome: First recurrence of syncope Raviele A.. Europace. 2001;3:336–341. Raviele A, et al. Eur Heart J. 2004;25:1741-1748.
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SYNPACE (Vasovagal SYNcope and PACing) Raviele A, et al. Eur Heart J. 2004;25:1741-1748. Results: 50% with pacing ON had recurrence vs. 38% with pacing OFF (not statistically significant) 0.6 0.7 0.8 0.9 1.0 0 200 400 600 800 1000 Pacemaker OFF % Syncope-Free p=0.58 0.5 0.4 0.3 0.2 0.1 0.0 Pacemaker ON Days Since Randomization
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INVASY (INotropy Controlled Pacing in VAsovagal Syncope) Objective: To evaluate Closed Loop Stimulation (CLS), a form of rate-adaptive pacing using RV impedance, in preventing recurrence of VVS Randomized, prospective, single-blind, multi-center N=50 patients 41: CLS therapy 9: Control (pacemaker programmed in DDI) Inclusion: Recurrent VVS and +HUT with cardioinhibition Primary outcome: Recurrence of two VVSs during a minimum of 1 year of follow-up Occhetta E, et al. Europace. 2004;6:538-547.
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INVASY (INotropy Controlled Pacing in VAsovagal SYncope) 20 40 60 0 100 % Syncope-Free P < 0.0001 Closed Loop Stimulation (CLS) Control (DDI only) Time Since Randomization 3m 6m 9m 1y 2y 3y Results: Patients with CLS had no syncope recurrence and improved quality of life Occhetta E, et al. Europace. 2004;6:538-547.