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Syncope A Diagnostic and Treatment Strategy

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. Transient Loss of Consciousness (TLOC). Syncope Neurally-mediated reflex syndromes

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Syncope A Diagnostic and Treatment Strategy

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  1. SyncopeA Diagnostic and Treatment Strategy David G. Benditt, M.D.University of Minnesota Medical SchoolMinneapolis, MN USA Richard Sutton, DScMed Royal Brompton Hospital London, UK

  2. Transient Loss of Consciousness (TLOC)

  3. 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” Classification of Transient Loss of Consciousness (TLOC) Real or Apparent TLOC Brignole M, et al. Europace, 2004;6:467-537.

  4. 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.

  5. Presentation Overview I. Etiology, Prevalence, Impact II. Diagnosis III. Specific Conditions and Treatment IV. Special Issues

  6. Section I:Etiology, Prevalence, Impact

  7. Causes of True Syncope Neurally- Mediated Orthostatic Cardiac Arrhythmia Structural Cardio- Pulmonary • 3 • Brady • SN Dysfunction • AV Block • • Tachy • VT • SVT • Long QT Syndrome • 1 • VVS • CSS • • Situational • Cough • Post- Micturition • 2 • Drug-Induced • • ANS Failure • Primary • Secondary • 4 • Acute Myocardial Ischemia • Aortic Stenosis • HCM • Pulmonary Hypertension • Aortic Dissection Unexplained Causes = Approximately 1/3 DG Benditt, MD. U of M Cardiac Arrhythmia Center

  8. 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.

  9. Impact of Syncope • 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%1eg, fractures, motor vehicle accidents • Minor injury in 29%1eg, lacerations, bruises 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.

  10. Impact of Syncope: US Trends Inpatient Trend* Physician Office Visits** (000s) (000s) *All patients discharged with syncope and collapse (ICD-9 Code:780.2) listed among diagnoses. **Syncope and collapse (ICD-9 Code: 780.2) listed as primary reason for visit. NHDS 2003. NAMCS 2002.

  11. Impact of Syncope: US Trends HospitalOutpatient Visits* EmergencyDepartment Visits* (000s) (000s) + + Not available *Syncope and collapse (ICD-9 Code:780.2) listed as primary reason for visit. NHAMCS 2002.

  12. 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.

  13. 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.

  14. Impact of Syncope: Quality of Life 73%1 71%2 60%2 Percent of Patients 37%2 Anxiety/Depression Alter DailyActivities RestrictedDriving ChangeEmployment 1Linzer M. J Clin Epidemiol. 1991;44:1037. 2Linzer M. J Gen Int Med. 1994;9:181.

  15. Quality of Life: UK Population Norms vs. Syncope Patients 49% 43% 37% 36% 26% % Prevalence 19% 9% 4% 3% 1% Mobility Usual Activities Self-Care Pain/Discomfort Anxiety/Depression Rose M, et al. J Clin Epidemiol. 2000;53:1209-1216.

  16. 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]

  17. 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 Implications of Syncope for Driving a Vehicle Olshansky B, Grubb B. In: Syncope: Mechanisms and Management. Futura. Armonk, NY. 1998. *Medtronic, Inc. Follow-up Forum. 1995/96;1(3):8-10.

  18. Challenges of Syncope • Diagnosis • Complex • Quality of life implications • Work • Mobility (automobiles) • Psychological • Cost • Cost/year • Cost/diagnosis

  19. Section II:Diagnosis

  20. 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

  21. 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.

  22. Diagnostic Flow Diagram for TLOC Initial Evaluation Syncope Not Syncope Certain Diagnosis Suspected Diagnosis Unexplained Syncope Confirm with Specific Test or Specialist Consultation Cardiac Likely Neurally-Mediated or Orthostatic Likely Frequent or Severe Episodes Single/Rare Episodes Cardiac Tests No Further Evaluation Tests for Neurally-Mediated Syncope Tests for Neurally-Mediated Syncope + - + - + - Re-Appraisal Re-Appraisal Treatment Treatment Treatment Treatment Brignole M, et al. Europace, 2004;6:467-537.

  23. 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.

  24. 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.

  25. 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 Carotid Sinus Massage (CSM) 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.

  26. 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.

  27. Heart Monitoring Options OPTION 10 Seconds 12-Lead 2 Days Holter Monitor Event Recorders(non-lead and loop) 7-30 Days Up to 14 Months ILR 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 TIME (Months) Brignole M, et al. Europace, 2004;6:467-537.

  28. Diagnostic Assessment: Yields(N=3411 to 4332) References Available

  29. Neurological Tests: Rarely Diagnostic for Syncope • EEG, Head CT, Head MRI • May help diagnose seizure Brignole M, et al. Europace. 2004;6:467-537.

  30. Head-Up Tilt Test (HUT) 60° - 80° • 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.

  31. Head-up Tilt Test Click once on image to play video. Carlos Morillo, MD, FRCPC Professor, Faculty of Health Sciences McMaster University, Hamilton Ontario

  32. Head-Up Tilt Test:ECG Leads and Intra-Arterial Pressure Tracing 2 1 DG Benditt, MD. U of M Cardiac Arrhythmia Center

  33. 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 Adenosine Triphosphate (ATP) Test Brignole M. Heart. 2000;83:24-28. Donateo P. J Am Coll Cardiol. 2003;41:93-98. Flammang D. Circ. 1999;99:2427-2433.

  34. 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

  35. Symptom-Rhythm Correlation with the ILR CASE: 56 year-old woman with refractory syncope accompanied with seizures. CASE: 65 year-old man with syncope accompanied by brief retrograde amnesia. Medtronic data on file.

  36. Randomized Assessment of Syncope Trial (RAST) 60 Patients Unexplained Syncope EF > 35% 30 Patients 30 Patients Conventional Testing(AECG, Tilt, EPS) PrimaryStrategy ILR 14 6 + + Diagnosis – – 1 8 + + Crossover ILR AECG, Tilt,EP Study 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.

  37. 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.

  38. 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.

  39. ISSUEInternational 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.

  40. ISSUEPatients with Isolated Syncope and Tilt-Positive Syncope 111 Patients with Syncope No SHD, Normal ECG Tilt Test Followed by Insertable Loop Recorder 82: Tilt-Negative “Isolated Syncope” 29: Tilt-Positive Follow-Up to Recurrent Spontaneous Episode Moya A. Circulation. 2001;104:1261-1267.

  41. ISSUEIsolated 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%) astilt-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.

  42. ISSUE Patients with Heart Disease and a Negative EP Test 35 Pts with Heart Diseaseand Insertable Loop Recorder Pre-Syncope: 13 Pts (37%) Syncope: 6 Pts (17%) ECG-Documented: 6 Pts (17%) ECG-Documented: 8 Pts (23%) 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 Menozzi C, et al. Circulation. 2002;105:2741-2745.

  43. ISSUEPatients 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.

  44. ISSUEPatients with Bundle Branch Block and Negative EP Test 52 Pts with BBBand Insertable Loop Recorder Syncope: 22 Pts (42%)* Stable AVB: 3 Pts (6%) Death: 1 Pt (2%) ILR-DetectedPre-Syncope:2 Pts (4%)** ILR-Detected: 19 Not Detected: 3 AVB: 2 (4%) AVB: 12 (63%) SA: 4 (21%) Asystole-undefined: 1 (5%) NSR: 1 (5%) Sinus tachy: 1 (5%) * 5 of these also had ≥1 presyncope ** Drop-out before primary-end point Brignole M., ET AL.,Circulation. 2001;104:2045-2050.

  45. ISSUEPatients 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.

  46. Section III:Specific Conditions and Treatment

  47. 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

  48. 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.

  49. “…cardiac syncope can be a harbinger of sudden death.” 1.0 0.8 0.6 0.4 0.2 0.0 Probability of Survival No Syncope Vasovagal andOther Causes Cardiac Cause 0 5 10 15 Follow-Up (yr) • 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.

  50. 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 Syncope Due to Structural Cardiovascular Disease: Principle Mechanisms Brignole M, et al. Europace. 2004;6:467-537.

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