Syncope A Diagnostic and Treatment Strategy

Syncope A Diagnostic and Treatment Strategy
Developed by: David G. Benditt, M.D Richard Sutton, DScMed University of Minnesota Medical Center Royal Brompton Hospital, London, UK

Presentation Overview
Prevalence & Impact Etiology Diagnosis & Evaluation Options Specific Conditions Treatment Options Insights into more efficient and effective diagnosis and treatment of patients with syncope

Section I: Prevalence and Impact

The Significance of Syncope
The only difference between syncope and sudden death is that in one you wake up.1 1 Engel GL. Psychologic stress, vasodepressor syncope, and sudden death. Ann Intern Med 1978; 89:

Syncope is a relatively common problem that affects over 1 million people in the U.S. each year. Syncope accounts for 1 to 6% of hospital admissions and 3% of emergency room visits each year.1,2 The incidence of syncope is greater than 500,000 new patients per year. 1.National Disease and Therapeutic Index on Syncope and Collapse, ICD-9-CM 780.2, IMS America, 1997. 2. Blanc J-J, L’Her C, Touiza A, et al. Prospective Evaluation and Outcome of Patients Admitted for Syncope Over a 1-Year Period. Eur Heart J, 2002; 23: 3.Day SC, et al. Evaluation and outcome of emergency room patients with transient loss of consciousness. Am J Med 1982;73:15-23. 4.Kapoor W. Evaluation and outcome of patients with syncope. Medicine 1990;69: 1 National Disease and Therapeutic Index on Syncope and Collapse, ICD-9-CM 780.2, IMS America, 1997 2 Blanc J-J, L’her C, Touiza A, et al. Eur Heart J, 2002; 23: 3 Day SC, et al, AM J of Med 1982 4 Kapoor W. Evaluation and outcome of patients with syncope. Medicine 1990;69:

Syncope Reported Frequency
Individuals <18 yrs Military Population yrs Individuals yrs* Individuals >70 yrs* 15% 20-25% 16-19% 23% Multiple reports have examined the frequency with which syncope occurs in various populations. This slide provides an overview of such findings. In essence the frequency with which syncope is reported to have occurred in various study groups is approximately 20%. The basis for syncope would be expected to differ substantially among these groups. Younger patients will have a greater proportion of vasovagal syncope, whereas older individuals may reasonably be expected to have a higher likelihood of underlying structural heart disease, and hence a greater predilection to more worrisome etiologies. Brignole M, Alboni P, Benditt DG, et al. “Guidelines on Management (Diagnosis and Treatment) of Syncope. Eur Heart J 2001; 22: *during a 10-year period Brignole M, Alboni P, Benditt DG, et al. Eur Heart J, 2001; 22:

explained: 53% to 62% infrequent, unexplained: 38% to 47% 1-4 Studies have shown that the cause of syncope remains undiagnosed in as many as 47% of the patients who present with this symptom. There are approximately 170,000 recurrent syncope patients in the U.S. today, meaning that up to 70,000 patients with recurrent, infrequent syncope may be going undiagnosed and therefore, improperly treated. Of these patients, 20,000 may have undergone extensive testing with no diagnosis. 1.Kapoor W. Evaluation and outcome of patients with syncope. Medicine 1990;69: 2.Silverstein M, et al. Patients with syncope admitted to medical intensive care units. JAMA 1982;248: 3.Martin G, et al. Prospective evaluation of syncope. Ann Emerg Med 1984;13: 4.Kapoor W, et al. A prospective evaluation and follow-up of patients with syncope. N Eng J Med 1983;309: 5.National Disease and Therapeutic Index, IMS America, Syncope and Collapse #780.2; Jan 1997-Dec 1997. 6.Kapoor W, et al. Diagnostic and prognostic implications of recurrences in patients with syncope. Am J Med 1987;83: 500,000 new syncope patients each year 5 170,000 have recurrent syncope 6 70,000 have recurrent, infrequent, unexplained syncope 1-4 1 Kapoor W, Med. 1990;69: 2 Silverstein M, et al. JAMA. 1982;248: 3 Martin G, et al. Ann Emerg. Med. 1984;12: 4 Kapoor W, et al. N Eng J Med. 1983;309: 5 National Disease and Therapeutic Index, IMS America, Syncope and Collapse #780.2; Jan 1997-Dec 1997. 6 Kapoor W, et al. Am J Med. 1987;83:

Some causes of syncope are potentially fatal Cardiac causes of syncope have the highest mortality rates Cardiac causes include both arrhythmias and structural heart problems, both of which contribute to high mortality rates. One of the goals, therefore, is to attempt to either rule out or rule in arrhythmic disorders. Syncope is a serious clinical problem with a reported mortality and major morbidity rate of over 7%.1 Among patients with an underlying cardiac cause of syncope, the reported 1-year mortality rate ranges from 18 to 33%.1-4 This means that within 5 years, most of the patients whose syncope has a cardiac cause will have died. 1.Day SC, et al. Evaluation and outcome of emergency room patients with transient loss of consciousness. Am J Med. 1982;73:15-23. 2.Kapoor W. Evaluation and outcome of patients with syncope. Medicine 1990;69: 3.Silverstein M, Singer D, Mulley A. Patients with syncope admitted to medical intensive care units. JAMA. 1982;248: 4.Martin G, Adams S, Martin H. Prospective evaluation of syncope. Ann Emerg Med. 1984;13: 1 Day SC, et al. Am J of Med 1982;73:15-23. 2 Kapoor W. Medicine 1990;69: 3 Silverstein M, Sager D, Mulley A. JAMA ;248: 4 Martin G, Adams S, Martin H. Ann Emerg Med. 1984;13:

Impact of Syncope 73% 1 71% 2 60% 2 Proportion of Patients 37% 2
Syncope result in substantial cost to patients and to society. For example, syncope patients live with lifestyle altering restrictions that affect daily activities, mobility, and employment. In addition, syncope and falling in the elderly commonly cause injury, institutionalization and premature death. Falls directly or indirectly cause 12% of deaths in geriatric population. (Baraff 1997). ____________________ Linzer M, Pontinen M, Gold DT, et al. Impairment of physical and psychological function in recurrent syncope. J Clin Epidemiol. 1991;44: Linzer M, Gold DT, Pontinen M, et al. Recurrent syncope as a chronic disease: Preliminary validation of a disease-specific measure of functional impairment. J Gen Int Med. 1994;9: Anxiety/ Depression Alter Daily Activities Restricted Driving Change Employment 1Linzer, J Clin Epidemiol, 1991. 2Linzer, J Gen Int Med, 1994.

Section II: Etiology

Syncope: A Symptom…Not a Diagnosis
Self-limited loss of consciousness and postural tone Relatively rapid onset Variable warning symptoms Spontaneous complete recovery Syncope should be considered as a symptom not as a diagnosis. The basis of syncopal symptoms should be sought through careful evaluation. Only after a cause is established can an effective treatment regimen be developed.

Causes of Syncope1 Cause Prevalence (Mean) % Prevalence (Range) %
Reflex-mediated: Vasovagal 18 8-37 Situational 5 1-8 Carotid Sinus 1 0-4 Orthostatic hypotension 8 4-10 Medications 3 1-7 Psychiatric 2 Neurological 10 3-32 Organic Heart Disease 4 Cardiac Arrhythmias 14 4-38 Unknown 34 13-41 These frequencies cited were based on the general experience reported in the literature at the time (circa 1998). Subsequently, diagnostic criteria and techniques have improved. Consequently, the numbers should be relied on only for “ballpark” estimates. 1Kapoor W. In Grubb B, Olshansky B (eds) Syncope: Mechanisms and Management. Armonk NY; Futura Publishing Co, Inc: 1998; 1-13.

Syncope: Etiology Neurally- Mediated Orthostatic Cardiac Arrhythmia
Structural Cardio- Pulmonary Non- Cardio- vascular 1 Vasovagal Carotid Sinus • Situational Cough Post- micturition 2 Drug Induced • ANS Failure Primary Secondary 3 Brady Sick sinus AV block • Tachy VT SVT Long QT Syndrome * 4 Aortic Stenosis HOCM • Pulmonary Hypertension 5 Psychogenic • Metabolic e.g. hyperventilation Neurological 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. 24% 11% 14% 4% 12% Unknown Cause = 34% DG Benditt, UM Cardiac Arrhythmia Center

Causes of Syncope-like States
Migraine* Acute hypoxemia* Hyperventilation* Somatization disorder (psychogenic syncope) Acute Intoxication (e.g., alcohol) Seizures Hypoglycemia Sleep disorders * may cause ‘true’ syncope

Section III: Diagnosis and Evaluation Options

Syncope Diagnostic Objectives
Distinguish ‘True’ Syncope from other ‘Loss of Consciousness’ spells: Seizures Psychiatric disturbances Establish the cause of syncope with sufficient certainty to: Assess prognosis confidently Initiate effective preventive treatment Syncope is often confused with other apparent loss of consciousness diagnoses. It is crucial to consider this distinction first, prior to embarking on a diagnostic evaluation.

Initial Evaluation (Clinic/Emergency Dept.)
Detailed history Physical examination 12-lead ECG Echocardiogram (as available) The first steps in the evaluation of the patient with syncope can be carried out in the clinic (The Initial Evaluation). A detailed medical history (especially focusing on syncope events) and careful physical examination often provide important clues. A 12-lead ECG and if necessary an echocardiogram are reasonably included at this stage. A careful Initial Evaluation may often provide a satisfactory diagnosis. In other cases, this Evaluation will permit more development of a cost-effective diagnostic strategy.

Syncope Basic Diagnostic Steps
Detailed History & Physical Document details of events Assess frequency, severity Obtain careful family history Heart disease present? Physical exam ECG: long QT, WPW, conduction system disease Echo: LV function, valve status, HOCM Follow a diagnostic plan... General rules for initiating the diagnostic evaluation of the syncope patient. The history must include detailed summary of events leading up to and following syncope events. Additionally, it is important to ascertain whether there is any evidence of underlying structural heart disease. The direction of subsequent evaluation differs in patients with and without heart disease.

Conventional Diagnostic Methods/Yield
Test/Procedure Yield (based on mean time to diagnosis of 5.1 months7 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 2% 7 External Loop Recorder (2-3 weeks duration) 20% 7 Insertable Loop Recorder (up to 14 months duration) 65-88% 6, 7 Neurological † (Head CT Scan, Carotid Doppler) 0-4% 4,5,8,9,10 A yield is defined as information that will point to more finely focused tests, specialties, or treatments. Patient history and physical exam are the most productive diagnostic tools for recurrent syncope, accounting for 49-85% of all syncope diagnoses.1,2 An ECG, also considered a first-line test, is diagnostic in 2-11% of cases.2 Beyond that, other tests have variable diagnostic yields. Holter monitors (worn for 1-3 days) capture ECGs during a syncopal episode in only 1% of patients, based on a mean time to recurrent event of 5.1 months.7 The effectiveness of tilt table tests, a common tool used to identify vasovagal syncope, depends on several factors, including patient selection and use of provocative drugs. Depending on these factors, the rate of positive tests has been reported in the range of 11-87%.3,5 However, about 10% or more of the population (who do not experience syncope) will have positive tilt table tests.4,6 External loop recorders (worn for 2-3 weeks) are most productive in motivated patients who experience relatively frequent syncope. They provide a diagnostic yield of 20%.7 Electrophysiology (EP) studies are generally more productive in patients with structural heart disease (SHD) and therefore are generally a higher priority for patients in this group.1 EP studies are used to diagnose syncope by inducing symptoms under controlled conditions, thereby attaining a “presumptive” diagnosis.1 EP testing usually fails to identify intermittent bradycardia as a cause of syncope (6%) and may sometimes reveal unrelated rhythm disturbances that may be mistakenly identified as the cause of syncope.2 1. Kapoor W, et al. A prospective evaluation and follow-up of patients with syncope. N Engl J Med 1983;309: 2. Kapoor W. Diagnostic evaluation of syncope. Amer J Med 1991;90: 3. Linzer M, et al. Clinical guideline: Diagnosing syncope: Part 2: Unexplained syncope. Ann Intern Med 1997;127:76-86. 4. Kapoor W. Evaluation and outcome of patients with syncope. Medicine 1990;69: 5. Kapoor W. Evaluation and management of the patient with syncope. JAMA 1992;268: 6. Krahn A, et al. The etiology of syncope in patients with negative tilt table and electrophysiological testing. Circulation 1995;92: Krahn A, Klein G, Yee R: Recurrent syncope. Experience with an implantable loop recorder. Cardiology Clinics 1997; 15(2): 8. Eagle K,, et al. The Yale J Biol and Medicine. 1983; 56: 1-8. 9. Day S, et al. Am J Med. 1982; 73: 10. Stetson P, et al. PACE. 1999; 22 (part II): 782. Please also see: Brignole M, Alboni P, Benditt DG, et al. “Guidelines on Management (Diagnosis and Treatment) of Syncope. Eur Heart Journal 2001; 22: 1 Kapoor, et al N Eng J Med, 1983. 2 Kapoor, Am J Med, 1991. 3 Linzer, et al. Ann Int. Med, 1997. 4 Kapoor, Medicine, 1990. 5 Kapoor, JAMA, 1992 6 Krahn, Circulation, 1995 7 Krahn, Cardiology Clinics, 1997. 8 Eagle K,, et al. The Yale J Biol and Medicine. 1983; 56: 1-8. 9 Day S, et al. Am J Med. 1982; 73: 10 Stetson P, et al. PACE. 1999; 22 (part II): 782. * Structural Heart Disease † MRI not studied

Syncope Evaluation and Differential Diagnosis
History – What to Look for Complete Description From patient and observers Type of Onset Duration of Attacks Posture Associated Symptoms Sequelae A comprehensive Medical History is key to the cost-effective diagnostic assessment of syncope patients. Critical historical features that need to be sought are listed here.

12-Lead ECG Normal or Abnormal? Short sampling window (approx. 12 sec)
Acute MI Severe Sinus Bradycardia/pause AV Block Tachyarrhythmia (SVT, VT) Preexcitation (WPW), Long QT, Brugada Short sampling window (approx. 12 sec) The 12-lead ECG samples only a brief period of the cardiac rhythm (about 12 s). Consequently, absence of an abnormal rhythm is not a useful observation. The 12-lead ECG may, however, offer some useful clues for the syncope evaluation. If present, the findings noted on this slide may help lead to the choice of appropriate additional tests.

Carotid Sinus Massage Site: Method:
Carotid arterial pulse just below thyroid cartilage Method: Right followed by left, pause between Massage, NOT occlusion Duration: 5-10 sec Posture – supine & erect Carotid sinus massage (CSM) is an often overlooked, yet highly cost effective test, especially in older syncope patients. CSM must be applied with care, and the method described here has proven both safe and effective. Note that an abnormal response to CSM (I.e., Carotid Sinus Hypersensitivity, CSH) is not diagnostic of Carotid Sinus Syndrome (CSS). Reproduction of symptoms is a crucial diagnostic element. To achieve symptom reproduction, it may be useful to conduct CSM with the patient in the upright posture. If the latter is to be done, the patient should be safely secured to a tilt table in order to prevent injury from a fall.

Carotid Sinus Syndrome (CSS)
Carotid Sinus Massage Outcome: 3 sec asystole and/or 50 mmHg fall in systolic blood pressure with reproduction of symptoms = Carotid Sinus Syndrome (CSS) Contraindications Carotid bruit, known significant carotid arterial disease, previous CVA, MI last 3 months Risks 1 in 5000 massages complicated by TIA Carotid sinus massage (CSM) is an often overlooked, yet highly cost effective test, especially in older syncope patients. CSM must be applied with care, and the method described here has proven both safe and effective. Note that an abnormal response to CSM (I.e., Carotid Sinus Hypersensitivity, CSH) is not diagnostic of Carotid Sinus Syndrome (CSS). Reproduction of symptoms is a crucial diagnostic element. To achieve symptom reproduction, it may be useful to conduct CSM with the patient in the upright posture. If the latter is to be done, the patient should be safely secured to a tilt table in order to prevent injury from a fall.

Conventional AECG Low Yield, Poor Symptom / Arrhythmia Concordance*
8 studies, 2612 patients 19% pts had symptoms with AECG Only 4% had arrhythmia with symptoms 79% pts were without symptoms 14% had arrhythmia despite absence of symptoms Ambulatory ECG recordings offer longer periods of ECG recording than are obtained by the conventional 12-lead ECG. Thus, the chance of detecting a transient arrhythmia is improved. Nonetheless, multiple studies indicate that conventional AECGs are not as effective as was once hoped. Newer AECG techniques are in evolution (e.g., implantable loop recorders [ILRs]), and their effectiveness may be greater (see RAST study slides). This slide summarizes data presented in an ACC/AHA Task Force report on AECG. Reference: Crawford MH, Bernstein SJ, Deedwania PC, et al, ACC/AHA Guidelines for Ambulatory Electrocardiography. J Am Coll Cardiol 1999;34: (Executive summary and recommendations. Circulation 1999;100: * ACC/AHA Task Force, JACC 1999;

Ambulatory ECG Method Comments Holter (24-48 hours)
Useful for infrequent events Event Recorder Limited value in sudden LOC Loop Recorder Implantable type more convenient (ILR) Wireless (internet) Event Monitoring In development The various forms of Ambulatory ECG recording techniques currently available are listed in this slide. ILRs are currently available. Internet monitoring is just being initiated, and although very promising, its utility is as yet uncertain.

Head-up Tilt Test (HUT)
Unmasks VVS susceptibility Reproduces symptoms Patient learns VVS warning symptoms Physician is better able to give prognostic / treatment advice The rationale for undertaking head-up tilt (HUT) testing in patients suspected of having vasovagal 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.

Head-Up Tilt Test (HUT)
ECG leads and intra-arterial pressure tracing illustrating the final moments of a head-up tilt test just prior to induced syncope. Note that blood pressure tended to fall in advance of the bradycardia component. Later, even though the patient is returned to supine posture,and the heart rate returns to normal, it may take some time for the arterial pressure to fully recover. The latter is due to persistent vasodilatation which may disappear slowly. DG Benditt, UM Cardiac Arrhythmia Center

Electroencephalogram
Not a first line of testing Syncope from Seizures Abnormal in the interval between two attacks – Epilepsy Normal – Syncope Neurologic studies (Head CT/MRI, EEG) are rarely useful in the diagnostic evaluation of the basis for syncope. Imaging may be justified if there is concern that syncope may have resulted in a head injury. Otherwise, absent apparent abnormal neurologic signs, such testing should be relegated to low priority.

Value of Event Recorder in Syncope
Example of a symptomatic wide-QRS tachycardia recorded during a near syncope in a patient undergoing AECG monitoring. *Asterisk denotes event marker Linzer M. Am J Cardiol. 1990;66:

Reveal® Plus Insertable Loop Recorder
The Reveal® Plus Insertable Loop Recorder system offers long-term, continuous, subcutaneous ECG monitoring and event-specific recording. This implantable device is designed to improve patient compliance with long-term AECG monitoring. The system includes an implanted loop recorder, a hand-held patient Activator, and a programmer with telemetry head that communicates noninvasively with the implanted device. When a patient experiences an episode, the device stores an ECG using the Activator or through the use of a auto-activating feature. The Reveal® Plus ILR can monitor continuously for up to 14 months. The probability of capturing an event is high—approximately 65-88%.1,2 The ECG captured during the episode may “reveal” the ECG during the patient’s episode or may allow the clinician to rule in or rule out arrhythmic causes. The stored ECG data is retrieved, viewed, and printed or saved to a disk, using a Medtronic 9790 programmer with a 9766 A or AL programmer head. The Reveal ILR can then be re-started for continued monitoring. Krahn A, et al. Final results from a pilot study with an insertable loop recorder to determine the etiology of syncope in patients with negative noninvasive and invasive testing. Am J Cardiol, 1998;82: 2. Krahn A, Klein GJ, Yee R, Skanes AC. Randomized assessment of syncope trial. Conventional diagnostic testing versus a prolonged monitoring strategy. Circulation 2001;104:46-51 Patient Activator Reveal® Plus ILR 9790 Programmer

ILR Recordings* 56 yo woman with syncope accompanied with seizures.
Infra-Hisian AV Block: Dual chamber pacemaker Examples of ECG recordings obtained by the Reveal® ILR system in 2 symptomatic patients. See associated text for details. 65 yo man with syncope accompanied with brief retrograde amnesia. VT and VF: ICD and meds *Medtronic data on file

Randomized Assessment of Syncope Trial
Usual care including: External loop recorder Tilt test, EPS and others Unexplained Syncope after history, physical exam, ECG, Holter Low Risk (EF > 35%) ILR Diagnosis + - Tilt test, EPS, others The Randomized Assessment of Syncope Trial (RAST) utilized the Reveal® ILR system to provide diagnostic information in syncope patients in whom the basis for symptoms remained unknown despite careful initial evaluation. Unexplained syncope patients were enrolled after meeting the inclusion/exclusion criteria, and were then randomized to ILR implantation or usual care (primary strategy) If a patient did not receive a diagnosis in the primary strategy arm, they were asked if they would accept crossover to the other study arm. Reference Krahn A, Klein GJ, Yee R, Skanes AC. Randomized assessment of syncope trial. Conventional diagnostic testing versus a prolonged monitoring strategy. Circulation 2001;104:46-51 Krahn A, Klein GJ, Skanes Y. Circulation 2001; 104:46-51.

RAST Methods Prospective randomized trial Inclusion: Exclusion:
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 one year of follow-up A brief summary of RAST methodology is provided here. Inclusion and Exclusion criteria are noted. Reference Krahn A, Klein GJ, Yee R, Skanes AC. Randomized assessment of syncope trial. Conventional diagnostic testing versus a prolonged monitoring strategy. Circulation 2001;104:46-51 Krahn A, Klein GJ, Skanes Y. Circulation 2001; 104:46-51.

RAST Results Unexplained Syncope n=60 ILR n=30 Conventional
Results of the initial phase of RAST are summarized here. Among patients randomized to ILR, there appeared to be greater diagnostic yield than in patients randomized to the conventional diagnostic pathway. In Follow-up n=3 Diagnosed n=14 Undiagnosed n=13 Diagnosed n=6 Undiagnosed n=24 Krahn A, Klein GJ, Skanes Y. Circulation 2001; 104:46-51.

RAST Crossover Results
Unexplained Syncope n=60 13/30 Undiagnosed after monitoring 6 accepted crossover to conventional 24/30 Undiagnosed after conventional 21 accepted crossover to ILR In RAST, patients who remained undiagnosed after completion of the first arm of the study (see preceding slide) were offered crossover to the other diagnostic strategy arm. Once again, ILR proved superior to the conventional diagnostic strategy Diagnosed n=1 Undiagnosed n=5 Diagnosed n=8 Undiagnosed n=5 In follow-up n=8 Krahn A, Klein GJ, Skanes Y. Circulation 2001; 104:46-51.

RAST - Diagnoses number of patients
Results show patients implanted with the ILR are more likely to receive a diagnosis in any category. The ILR was almost 5 times better at detecting bradycardia compared to conventional testing. Reference Krahn A, Klein GJ, Yee R, Skanes AC. Randomized assessment of syncope trial. Conventional diagnostic testing versus a prolonged monitoring strategy. Circulation 2001;104:46-51 Krahn A, Klein GJ, Skanes Y. Circulation 2001; 104:46-51.

Conventional EP Testing in Syncope
Limited utility in syncope evaluation Most useful in patients with structural heart disease Heart disease…… % No Heart disease…18-50% Relatively ineffective for assessing bradyarrhythmias Conventional EP testing (I.e.,EPS, electrical stimulation without autonomic studies such as HUT) has not been highly effective in substantiating a basis for syncope. In this regard, EPS has been more effective in patients with structural cardiovascular disease than in those with normal cardiovascular status. Further, EPS has been more effective in patients with tachyarrhythmias than in those with bradyarrhythmias. The most important findings at EPS in regard to the evaluation of syncope patients are listed on the next slide. Brignole M, Alboni P, Benditt DG, et al. “Guidelines on Management (Diagnosis and Treatment) of Syncope. Eur Heart Journal 2001; 22: Brignole M, Alboni P, Benditt DG, et al. Eur Heart Journal 2001; 22:

EP Testing in Syncope: Useful Diagnostic Observations
Inducible monomorphic VT SNRT > 3000 ms or CSRT > 600 ms Inducible SVT with hypotension HV interval ≥ 100 ms (especially in absence of inducible VT) Pacing induced infra-nodal block Although EPS may not be as helpful as was once thought in terms of the diagnostic evaluation of syncope patients, the findings listed here are of particular value

International Study of Syncope of Uncertain Etiology
ISSUE Study International Study of Syncope of Uncertain Etiology Objectives: Understand the mechanism of syncope in tilt-positive and tilt-negative (isolated) patients Use the ILR to assess the correlation of rhythms captured during tilt testing and spontaneous recurrent episodes Inclusion Criteria: Patients with three or more syncopal episodes in the last 2 years Groups matched in age, sex, history of syncope, ECG, Echo abnormalities, SHD and arrhythmias Moya A. Circulation. 2001; 104:

ISSUE Study Design Multicenter, prospective 111 syncope patients
3 episodes in 2 years, first and last episode >6 months apart History, physical exam, ECG, CSM, echo, Holter (24 hr), other tests as appropriate Tilt test followed by implant of Reveal Insertable Loop Recorder Follow-up to recurrent spontaneous episode Moya A. Circulation. 2001; 104:

ISSUE Study Results Results Tilt-Negative Syncope (Isolated) n=82
Tilt-Positive Syncope n=29 Recurrent Event Occurrence (#) 34% (28) 34% (10) Mean Time to Recurrent Event (range) 105 days (47-226) 59 (22-98) ILR ECG Documented (#) 29% (24) 28% (8) Tachyarrhythmia 2% (2) Bradycardia 16% (13) 21% (6) Sinus Brady 3% (1) Sinus Arrest 12% (10) 17% (5) AV Block 1% (1) Total Arrhythmic 18% (15) Normal Sinus Rhythm 11% (9) 7% (2) Moya A. Circulation. 2001; 104:

ISSUE Study Conclusions:
Homogeneous findings from tilt-negative and tilt-positive syncope patients were observed (clinical characteristics and outcomes). Most frequent finding was asystole secondary to progressive sinus bradycardia, suggesting a neuromediated origin In this study tilt-negative patients had as many arrhythmias (18%) as tilt-positive patients (21%) In tilt-positive patients the spontaneous episode ECG was more frequently asystolic than what was predicted by tilt test Moya A. Circulation. 2001; 104:

ISSUE Study Implications
HUT outcome was not predictive of vasodepressor vs. cardioinhibitory response Bradycardia is common in spontaneous VVS - independent of HUT outcome Bradycardia is more prevalent in spontaneous events vs. HUT induced VVS Clinical Implication: Consider a strategy of postponing treatment until a spontaneous episode can be documented The ISSUE study used ILR to assess diagnosis in patients with suspected vasovagal syncope who had undergone head-up tilt-table (HUT) testing. Findings revealed a much higher frequency of bradycardia in conjunction with spontaneous syncope than would have been predicted based on HUT findings. Reference: Moya A, Brignole M, Menozzi C, Garcia-Civera R, Tognarini S, Mont L, Botto G, Giada F, Cornacchia D, and ISSUE Investigators. Mechanism of syncope in patients with isolated syncope and in patients with tilt-positive syncope. Circulation 2001;104: Moya A. Circulation. 2001; 104:

Symptom-Rhythm Correlation
Auto Activation Point Patient Activation Point The gold standard for determining if a syncope episode is due to an arrhythmia is to record the rhythm during symptoms (symptom rhythm correlation). The ILR may help rule-in or rule-out arrhythmogenic causes. This slide depicts findings from an ILR interrogation as they appear on the programmer screen. In order to view stored event data, one taps the screen with the touch pen on the area of the summary graph that one wishes to view in more detail. This takes the viewer to the first zoom level of the event ECG waveform data and centers the area of the event you tapped. To view the event in greater detail, one taps the screen over the ECG of interest. On-screen calipers are available at every zoom level to measure cycle length. Intervals can be measured in milliseconds or beats per minute. Note: A - represents auto activated event P - indicates time patient activated the event

Diagnostic Limitations
Difficult to correlate spontaneous events and laboratory findings Often must settle for an attributable cause Unknowns remain 20-30% 1 Determining a definitive basis for syncope can often be frustrating. Patience is a necessity. However, not infrequently one must settle for the most reasonable ‘attributable’ cause. 1Kapoor W. In Grubb B, Olshansky B (eds) Syncope: Mechanisms and Management. Armonk NY; Futura Publishing Co, Inc: 1998; 1-13.

Unexplained Syncope Diagnosis
History and Physical Exam Surface ECG ENT Evaluation Endocrine Evaluation CV Syncope Workup Holter ELR or ILR Tilt Table Echo EPS Neurological Testing Head CT Scan Carotid Doppler MRI Skull Films Brain Scan EEG Other CV Testing Angiogram Exercise Test SAECG Searching for a Diagnosis: Patients can enter the diagnostic process at various points based on their presenting symptoms and/or syncope-related injuries. Also, the process of deriving a diagnosis for syncope can vary from institution to institution. As noted earlier, the diagnosis of syncope begins with a patient history and physical, and a surface electrocardiogram recording. If this initial evaluation suggests a cardiovascular cause such as myocardial infarction or structural heart disease, an echocardiogram and EP study may be performed. If no diagnosis is reached with these tests, the physician may move to any of the following tests, in any order: tilt table testing, Holter monitor, external loop recorder (ELR), or Reveal® Plus Insertable Loop Recorder(IRL). If none of those tests yield a diagnosis, some tests may be performed repeatedly and/or other specialists might be consulted for further testing including: endocrinology, neurology, psychiatry, ENT, etc. If no structural cardiovascular problems are suspected, the physician may choose diagnostic testing based on suspected vasovagal etiology and frequency and severity of symptoms. New diagnostic tools, such as ILRs, will cause significant discussions about when to use them, given their high diagnostic yields and high patient compliance. NOTES: ECG: Electrocardiogram EEG: Electroencephalogram MRI: Magnetic Resonance Imaging Echo: Echocardiogram EP Study: Electrophysiology Study MI: Myocardial Infarction SHD: Structural Heart Disease ENT: ears-nose-throat Psychological Evaluation Adapted from: W.Kapoor.An overview of the evaluation and management of syncope. From Grubb B, Olshansky B (eds) Syncope: Mechanisms and Management. Armonk, NY: Futura Publishing Co., Inc.1998.

Typical Cardiovascular Diagnostic Pathway
Syncope History and Physical, ECG Known SHD No SHD > 30 days; > 2 Events < 30 days Echo This flow chart shows a typical sequence of testing, patients may undergo in search of a diagnosis. SHD (Structural Heart Disease) EPS Tilt Holter/ ELR ILR Tilt ILR - + Tilt/ILR Treat Adapted from: Linzer M, et al. Annals of Int Med, :76-86. Syncope: Mechanisms and Management. Grubb B, Olshansky B (eds) Futura Publishing 1999 Zimetbaum P, Josephson M. Annals of Int Med, : Krahn A et al. ACC Current Journal Review,1999. Jan/Feb:80-84.

Section IV: Specific Conditions
The next session of this set deals with some of the more important causes of syncope. Specific conditions are dealt with approximately in the order of the frequency with which they may be expected to occur in clinical practice.

Neurally-Mediated Reflex Syncope (NMS)
Vasovagal syncope (VVS) Carotid sinus syndrome (CSS) Situational syncope post-micturition cough swallow defecation blood drawing etc. The neurally-mediated reflex causes of syncope are a group of related conditions in terms of symptomatic hypotension being caused by a variable combination of bradycardia and vasodilatation. Vasovagal syncope and carotid sinus syndrome are the most frequent conditions in this group. The others occur from time-to-time and are usually recognized only if a detailed medical history is obtained.

NM Reflex Syncope: Pathophysiology
Multiple triggers Variable contribution of vasodilatation and bradycardia Neurally-mediated reflex syncope can be triggered by a wide variety of situations (thus the commonly used term ‘situational’ syncope). Extended periods of upright posture, and medical procedures, are among the more common situations associated with vasovagal faints.

NMS – Basic Pathophysiology
Cerebral Cortex Vascular Bed Bradycardia/ Hypotension Baro- receptors Heart Feedback via Carotid Baroreceptors Other Mechanoreceptors Parasympathetic (+) sympathetic (+) ¯ Heart Rate ¯ AV Conduction _ Vasodilatation Physiology of Fainting The physiology of the common faint is depicted graphically in this slide (based on Figure 1 in Benditt 1996). The afferent trigger signals (e.g., pain, emotional upset, dehydration) are not depicted. The efferent loop of the neural reflex comprises: Parasympathetic signals from the cerebral cortex drive heart rate down and slow (or even block) AV conduction. Sympathetic signals increase dilation of the vascular bed. Bradycardia and/or hypotension result. Carotid baroreceptors and other mechanoreceptors sense effects driven by parasympathetic and sympathetic systems and provide paradoxical feedback to the central nervous system. The result may be a downward spiral in heart rate and blood pressure leading to syncope. __________________ Benditt DG, Lurie KG, Adler SW, et al. Pathophysiology of vasovagal syncope. In: Neurally mediated syncope: Pathophysiology, investigations and treatment. Blanc JJ, Benditt D, Sutton R. Bakken Research Center Series, v. 10. Armonk, NY: Futura, 1996. Benditt DG, Lurie KG, Adler SW, et al. Pathophysiology of vasovagal syncope. In: Neurally mediated syncope: Pathophysiology, investigations and treatment. Blanc JJ, Benditt D, Sutton R. Bakken Research Center Series, v. 10. Armonk, NY: Futura, 1996

Vasovagal Syncope (VVS): Clinical Pathophysiology
Neurally Mediated Physiologic Reflex Mechanism with two Components: Cardioinhibitory ( HR ) Vasodepressor ( BP ) Both components are usually present Syncope in vasovagal fainters, as in other forms of neurally-mediated reflex syncope, is due to systemic hypotension resulting in a transient period of inadequate cerebral blood flow. Hypotension is the result of 2 pathophysiologic components: 1. Marked bradycardia or inappropriately slow heart rate for the blood pressure (i.e., cardioinhibitory feature) 2. Vasodilatation The relative contribution of these 2 components varies among patients

Prevalence of VVS Prevalence is poorly known In general:
Various studies report 8% to 37% (mean 18%) of cases of syncope (Linzer 1997) In general: VVS patients younger than CSS patients Ages range from adolescence to elderly (median 43 years) Pallor, nausea, sweating, palpitations are common Amnesia for warning symptoms in older patients Prevalence of VVS The prevalence of VVS is poorly known. The published data that exists mostly dates from before the advent of tilt table testing. Linzer (1997) surveyed the literature and found published prevalences varying from 8% to 37% (mean 18%) of cases of syncope. Standards for diagnosis and reporting still are emerging. It is generally recognized that VVS patients usually are younger than CSS patients (age range is from adolescent to elderly, median 43 years) VVS is more common in females. ____________________ Linzer MD, Yang EH, Estes M, et al. Diagnosing syncope. Part 1: Value of history, physical examination, and electrocardiography. Ann Into Med. 1997;126(12):

Spontaneous VVS 16.3 sec Continuous Tracing 1 sec
Example of marked bradycardia recorder during a spontaneous vasovagal faint. The asystolic periods may be impressive in their duration, but do not in themselves constitute an indication for cardiac pacing. Continuous Tracing 1 sec DG Benditt, UM Cardiac Arrhythmia Center

Management Strategies for VVS
Optimal management strategies for VVS are a source of debate Patient education, reassurance, instruction Fluids, salt, diet Tilt Training Support hose Drug therapies Pacing Class II indication for VVS patients with positive HUT and cardioinhibitory or mixed reflex Management Strategies for VVS Optimal management strategies for VVS are a source of debate. Patient education, reassurance, and instruction. When the patient has a relatively long prodrome, evasive action may prevent injury if not syncope. Control of fluids, salt, and diet may help reduce incidence. Support hose may limit blood pooling in the legs and feet. Drug therapy should be used as a second line option. Midodrine and beta-adrenergic blockers are the agents most thoroughly studied to date/ Pacing may benefit some patients Pacing today is generally considered a last resort unless the patient experiences prolonged asystole during episodes. Diagnosis of VVS with positive head-up tilt test and a cardioinhibitory or mixed reflex is a Class II indication for pacing. 2 large randomized controlled trials support the utility of pacing in very symptomatic VVS patients

VVS: Tilt-Training Objectives Technique Enhance Orthostatic Tolerance
Diminish Excessive Autonomic Reflex Activity Reduce Syncope Susceptibility / Recurrences Technique Prescribed Periods of Upright Posture Progressive Increased Duration Head-up tilt testing (HUT) has proved to be of considerable clinical value in establishing susceptibility to VVS in syncope patients. As with any test, the observations during HUT must be considered in the light of all clinical data in a given patient.

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 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:

Etiology of CSS Sensory nerve endings in the carotid sinus walls respond to deformation “Deafferentation” of neck muscles may contribute Increased afferent signals to brain stem Reflex increase in efferent vagal activity and diminution of sympathetic tone results in bradycardia and vasodilation 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. Differentiation 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 Kenny RA, McIntosh SJ. Carotid sinus syndrome. In: Syncope in the older patient. Kenny RA (ed). London: Chapman & Hall Medical, 1996, pp Carotid Sinus

Carotid Sinus Hypersensitivity(CSH)
Abnormal response to CSM Absence of symptoms attributable to CSS CSH reported frequent in ‘fallers’ (Kenny) CSH  CSS 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: Katritsis D, Ward DE, Camm AJ. Can we treat carotid sinus syndrome? PACE. 1991;14(9): 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.

CSS and Falls in the Elderly
30% of people >65 yrs of age fall each year1 Total is 9,000,000 people in USA Approximately 10% of falls in elderly persons are due to syncope2 50% of fallers have documented recurrence3 Prevalence of CSS among frequent and unexplained fallers unknown but… CSH present in 23% of >50 yrs fallers presenting at ER 3 CSS and Falls in the Elderly Falls are the leading cause of injury among the elderly. According to “Falling in the Elderly” (1995): 30% of the population older than 65 years of age falls each year. In the U.S., that amounts to about 9,000,000 people. 50% of these fallers have documented recurrence. 8% of the population greater than 70 years of age visit an ER for a fall. 40% of these visits result in hospitalization. What is the contribution of cardioinhibitory CSS to these falls? This is an area of active research, but already-published results are suggestive: In one study, 279 fallers 50 years or older presenting to an emergency room with frequent or unexplained falls (at least 3 in previous 12 months) underwent carotid sinus massage, and 65 (23%) exhibited cardioinhibitory carotid sinus hypersensitivity (Richardson 1997). ____________________ Falling in the Elderly: U.S. Prevalence Data. Journal of the American Geriatric Society, December, 1995. Richardson DA, Bexton RS, Shaw FE, Kenny RA. Prevalence of cardioinhibitory carotid sinus hypersensitivity in patients 50 years or over presenting to the Accident and Emergency Department with “unexplained” or “recurrent” falls. PACE March 1997 (Part II): 1Falling in the Elderly: U.S. Prevalence Data. Journal of the American Geriatric Society, 2 Campbell et al: Age and Aging 1981;10: 3Richardson DA, Bexton RS, et al. Prevalence of cardioinhibitory carotid sinus hypersensitivity in patients 50 years or over presenting to the Accident and Emergency Department with “unexplained” or “recurrent” falls. PACE 1997

Section V: Treatment Options

VVS: Pharmacologic Rx Salt /Volume Beta-adrenergic blockers
Salt tablets, ‘sport’ drinks, fludrocortisone Beta-adrenergic blockers 1 positive controlled trial (atenolol), 1 on-going RCT (POST) Disopyramide SSRIs 1 controlled trial Vasoconstrictors (e.g., midodrine) 1 negative controlled trial (etilephrine) This slide summarizes the key pharmacologic treatment options in VVS patients. Salt/volume education in conjunction with reassurance and/or tilt-training are the primary treatment avenues. Drug therapy should be reserved as a second-line option.

Midodrine for Neurocardiogenic Syncope
Months p < 0.001 Symptom – Free Interval 180 160 140 120 100 80 60 40 20 Fluid Midodrine Findings from a recent clinical trial in which salt/volume therapy and midodrine treatment were compared in VVS patients. Midodrine proved to be more effective than volume alone in this selected patient population. Journal of Cardiovascular Electrophysiology Vol. 12, No. 8, Perez-Lugones, et al.

Role of Pacing in Treating VVS
Status of Pacing in VVS Perception of pacing for VVS changing: VVS with +HUT and cardioinhibitory response a Class IIb indication1 Recent clinical studies demonstrated benefits of pacing in select VVS patients: VPS I VASIS SYDIT VPS II –Phase I ROME VVS Trial Role of Pacing in Treating VVS The perception of pacing as therapy for selected VVS patients has been changing with increased understanding of the syndrome, improved diagnostic techniques (especially tilt testing), and the development of improved therapies. VVS with a positive head-up tilt test and a predominately cardioinhibitory response may be considered a Class II indication for pacing. DDD/DDI with rate hysteresis sometimes has been successful, although it suffers from limitations: It uses a hysteresis rate as a trigger and a relatively high lower rate for intervention. “False positives” may result in prolonged high rate intervention. In recent years, new rate drop therapies specifically designed for treatment of neurocardiogenic syncope have been introduced. 1Gregoratos G, et al. ACC/AHA Guidelines for Implantation of Cardiac Pacemakers and Antiarrhythmic Devices. Circulation ; 97:

Role of Pacing in Treating VVS
Status of Pacing in VVS Benefits of specific device features evolving: Some success with DDD/DDI hysteresis 1 “False positives” may result in prolonged high rate intervention Tied to lower rate intervention Rate drop therapies designed for treating VVS syncope appear to be successful 2-4 Role of Pacing in Treating VVS The perception of pacing as therapy for selected VVS patients has been changing with increased understanding of the syndrome, improved diagnostic techniques (especially tilt testing), and the development of improved therapies. VVS with a positive head-up tilt test and a predominately cardioinhibitory response may be considered a Class II indication for pacing. DDD/DDI with rate hysteresis sometimes has been successful, although it suffers from limitations: It uses a hysteresis rate as a trigger and a relatively high lower rate for intervention. Limited in response to “False positives” In recent years, new rate drop therapies specifically designed for treatment of neurocardiogenic syncope have been introduced. 1 Sutton R, et al. Circulation ; 102: 2 Connolly S, et al. J Am Coll Cardiol 1999; 33:16-20. 3 Ammirati F, et al. Circulation. 2002; 104: 4 Ammirati F, et al. NASPE Abstract #307. PACE, Vol. 24, April 2002, Part II.

VPS-I Vasovagal Pacemaker Study I
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 +HUT Relative bradycardia* *a trough heart rate <60/min if no isoproterenol used, <70/min if up to 2 mcg/min isoproterenol used, or <80/min if over 2 mcg/min isoproterenol used Connolly S, et al. J Am Coll Cardiol 1999; 33:

Endpoints: Outcome: VPS- I Time to first syncope RESULTS PACEMAKER
CONTROL (n=27) Number of patients w/syncopal recurrence 6 (22%) 19 (70%) Mean time to first recurrence (days) 112 54 Relative risk reduction of syncope* 85.4% - *2p = Connolly S, et al. J Am Coll Cardiol 1999; 33:

VPS- I 100 90 80 Control (No Pacemaker) 70 60 Cumulative Risk (%) 50
40 30 Pacemaker 20 10 3 6 9 12 15 Time in Months Number At Risk C P Connolly S, et al. J Am Coll Cardiol 1999; 33:

VPS-I Conclusion: Dual-chamber pacing with rate drop response
reduces the likelihood of syncope in patients with recurrent VVS. Connolly S, et al. J Am Coll Cardiol 1999; 33:

VASIS Vasovagal Syncope International Study
Study Design: 42 patients, randomized, prospective, multicenter 19 DDI pacemaker (80 bpm) with rate hysteresis (45 bpm) 23 no pacemaker Patient Inclusion Criteria: > 3 syncopal events in 2 years and last event occurring within 6 months of enrollment and, Positive VASIS type 2A or 2B cardioinhibitory response to HUT and, Age > 40 years or drug refractory if < 40 years Type 2A response is defined as the heart rate rising initially then falling to a ventricular rate <40 bpm for >10 sec or asystole occurring for >3 sec, with blood pressure rising initially then falling before the heart rate falls. Type 2B response is defined as the heart rate rising initially then falling to a ventricular rate <40 bpm for >10 sec or asystole occurring for >3 sec, with blood pressure rising initially and only falling to hypotensive levels <80 mmHg systolic at or after the onset of rapid and severe heart rate fall. Sutton, R, et al. Circulation ; 102:

Endpoints: Outcome: VASIS Time to first syncope RESULTS Pacemaker
No Pacemaker (n=23) Number of patients w/syncopal recurrence 1 (5%) 14 (61%) Median time to first recurrence (months)* 15 5 *P= Sutton, R, et al. Circulation ; 102:

VASIS 100 Pacemaker 80 p=0.0004 % syncope-free 60 40 No-Pacemaker 20 2
The VASIS trial examined the effectiveness of cardiac pacing in patients with recurrent VVS symptoms and evidence of a bradycardiac component during evaluation. As was the case in the North American VPS1 study, pacing was more effective than conventional therapy in terms of preventing syncope recurrences. The VASIS intention-to-treat data are presented in Kaplan-Meier format. References: VASIS: Sutton R, Brignole M, Menozzi C, et al. Dual-chamber pacing is efficacious in treatment of neurally-mediated tilt-positive cardioinhibitory syncope. Pacemaker versus no therapy: a multicenter randomized study. Circulation 2000; 102: VPS1: Connolly SJ, Sheldon R, Roberts RS, Gent M, Vasovagal pacemaker study investigators. The North American vasovagal pacemaker study (VPS): A randomized trial of permanent cardiac pacing for the prevention of vasovagal syncope. J Am Coll Cardiol 1999; 33: 16-20 2 3 4 5 6 Years 7 12 14 15 23 31 40 # of pts Sutton, R, et al. Circulation ; 102:

VASIS Conclusion: Dual-chamber pacing (at a rate of 80 bpm ) with rate hysteresis reduces the likelihood of syncope in patients with tilt-positive, cardioinhibitory syncope. Sutton, R, et al. Circulation ; 102:

SYDIT Syncope Diagnosis and Treatment Study
Study Design: 93 patients randomized, prospective, multicenter 46 DDD pacemaker with rate drop response (RDR) 47 Atenolol 100 MG/D Patient Inclusion Criteria: > 55 yrs > 3 syncopal episodes in 2 years + HUT with relative bradycardia (trough HR <60 bpm) A recent study compared cardiac pacing (DDD mode with rate-drop response algorithm [RDR]) to beta-adrenergic blockade (atenolol 100 mgm daily) in older (>55 years) patients with VVS and evidence of bradycardia. The primary endpoint was time to first syncope recurrence. Ammirati F, et al. Circulation. 2001; 104:52-57.

SYDIT Endpoints: Outcome: Time to first syncope RESULTS PACED (n= 46)
DRUG (n= 47) Number of patients w/syncopal recurrence* 2 (4%) 12 (25%) Median time to first recurrence (days) 390 135 Pacing proved to be more effective (see slide for data). REFERENCE Ammirati F, Colivicchi F, Santini M, et al. Permanent cardiac pacing versus medical treatment for the prevention of recurrent vasovagal syncope. A multicenter, randomized, controlled trial. Circulation 2001; 104: 52-56 *P=0.004 Ammirati, et al. Circulation. 2001; 104:52-57.

Syncope-free Survival: Intention-to-Treat (n=46/paced, 47/drug).
SYDIT Syncope-free Survival: Intention-to-Treat (n=46/paced, 47/drug). 1.0 0.9 drug pacemaker 0.8 P = % of syncope free pts Data from the pacing vs. atenolol study discussed on the previous slide. Findings are depicted in terms of % patients remaining syncope-free vs. time (days). In general, pacemaker treated patients (pmk) had a longer symptom free interval than did drug treated patients. 0.7 0.6 100 200 300 400 500 600 700 800 900 1000 Time (days) Ammirati F, et al. Circulation. 2001; 104:52-57.

SYDIT Conclusion: Dual-chamber pacing + RDR is superior to Atenolol in prevention of recurrent syncope in highly symptomatic patients with relative bradycardia during tilt-induced syncope. Ammirati F, et al. Circulation. 2001; 104:52-57.

VPS-II: Phase I Vasovagal Pacemaker Study-II
Study Design: 100 patients, randomized, prospective, multicenter 50 DDD pacemaker with rate drop response (RDR) 50 ODO pacemaker (inactive mode) Patient Inclusion Criteria: > 6 syncope events ever or > 3 syncope events in 2 years or > 1 syncope event in 6 months and, Positive HUT with syncope or presyncope and a heart rate blood pressure product <9000 Presented at the 23rd Annual Scientific Sessions of the North American Society of Pacing and Electrophysiology. Late Breaking Clinical Trials, May 11,

VPS-II: Phase I Endpoints: Outcome: Time to first syncope RESULTS
DDD Pacemaker (n= 50) ODO Pacemaker Number of patients w/syncopal recurrence 16 (32%) 22 (44%) Relative Risk Reduction* 28.7% - *P=0.153 Presented at the 23rd Annual Scientific Sessions of the North American Society of Pacing and Electrophysiology. Late Breaking Clinical Trials, May 11,

Cumulative Risk of Syncope
VPS-II: Phase I 0.4 0.3 ODO DDD Cumulative Risk of Syncope 0.2 P = (one-sided) 0.1 0.0 1 2 3 4 5 6 ODO DDD Number at Risk Presented at the 23rd Annual Scientific Sessions of the North American Society of Pacing and Electrophysiology. Late Breaking Clinical Trials, May 11,

Conclusions: VPS-II: Phase I
Lower than anticipated syncope event rate in the control arm. Higher than anticipated event rate in the treatment group. Consequence: treatment effect was less than VPS-I. Results favored pacing but the treatment effect was not statistically significant. Presented at the 23rd Annual Scientific Sessions of the North American Society of Pacing and Electrophysiology. Late Breaking Clinical Trials, May 11,

VVS Pacing Trials Conclusions
DDD pacing reduces the risk of syncope in patients with recurrent, refractory, highly-symptomatic, cardioinhibitory vasovagal syncope.

SAFE PACE Study Design Randomized controlled trial (N=175):
Pacing (87) vs. No Pacing (88) Single center: Royal Victoria Infirmary, Newcastle, UK Recruitment began: April 1998 12 month follow-up per patient Study concluded: May 2000 The study was a randomised controlled trial, pacing versus no pacing, performed at the Royal Victoria Infirmary in Newcastle, between April 1998 and May Patients were followed for 12 months after randomisation. Kenny RA, J Am Coll Cardiol 2001; 38:

SAFE PACE Inclusion Criteria
Consecutive adults attending accident and emergency department > 50 Years - Experienced non-accidental fall Positive response to CSM The inclusion criteria were consecutive adults, over the age of 50 years, presenting with a non-accidental fall, and who exhibited a positive response to CSM and who had no evidence of cognitive impairment or dementia. Kenny RA, J Am Coll Cardiol 2001; 38:

SAFE PACE Screening Process
Accident and Emergency Attendees > 50 Yrs Falls or Syncope Non-accidental Fall CSM Performed The study design is shown in the next slide. Patients presenting the A & E Department (or ER) were screened for falls or syncope, and non-accidental fallers identified. Carotid sinus massage was performed, and those patients who exhibited a cardioinhibitory or mixed (i.e. both vasodepressor and cardioinhibitory) response were randomised to either pacing or no specific intervention. Cardioinhibitory or Mixed CSH RCT Control Pacemaker Kenny RA, J Am Coll Cardiol 2001; 38: 25

SAFE PACE Screening Results
RCT (n=175) Control (n=88) Pacemaker (n=87) Patients in the pacing arm of the study received a Medtronic DR pacemaker, containing the rate-drop response algorithm for syncope patients. No pacing intervention Medtronic Thera DR (Rate Drop Response Algorithm) Kenny RA, J Am Coll Cardiol 2001; 38: 25

SAFE PACE Results Number of Falls
Control n=87 Pacemaker n=84 % Participants w/Falls 60% 58% Total Number of Falls* 699 216 Mean Number of Falls** 9.3 4.1 70% Reduction [OR 0.42; 95% CI: 0.23, 0.75] However, there was a statistically significant reduction in the total number of falls among the pacemaker patient group, with a 70% reduction in total falls compared with the control group. * Falls during 12 months post randomization ** Crude adjustment calculation Kenny RA, J Am Coll Cardiol 2001; 38:

SAFE PACE Results Number of Syncopal Episodes
Control N=87 Pacemaker N=84 % Participants w/Syncopal Events 22% 11% Total Number of Syncopal Events 47 22 Mean Number Syncopal Events 1.14 0.20 50% Reduction [OR 0.53; 95% CI 0.23; 1.20 ns] Only 28 patients reported syncope; 22 syncopal events were reported by paced patients and 47 by controls. Although there was a 50% reduction in the overall number of syncopal episodes, this did not reach statistical significance. * Syncopal events 12 months past randomization ** Crude adjustment calculation Kenny RA, J Am Coll Cardiol 2001; 38:

SAFE PACE Results Number of Injury Events
Control n= 87 Pacemaker n= 84 % Participants w/Injurious Events 41% 35% Total Number Injury Events 202 61 -Fractures -Soft Tissue Injury 4 198 3 58 70% Reduction There was also a reduction in the total number of injury events of 70%, from 202 in the control group to 61 in paced patients. * Injurious events 12 months post randomization Kenny RA, J Am Coll Cardiol 2001; 38:

SAFE PACE Conclusions Falls by 70% Syncopal events by 53%
In patients with unexplained falls and a diagnosis of Cardioinhibitory CSH, cardiac pacing reduced the total number of: Falls by 70% Syncopal events by 53% Injurious events by 70% In patients with unexplained falls and a diagnosis of cardioinhibitory carotid sinus hypersensitivity, cardiac pacing reduced the total number of falls by 70%, total syncopal events by 53% and total injurious events by 70%. Kenny RA, J Am Coll Cardiol 2001; 38:

Role of Pacing in CSS -- Syncope Recurrence Rate
Class I indication for pacing (AHA and BPEG) Limit pacing to CSS that is: Cardioinhibitory Mixed DDD/DDI superior to VVI 57% % Recurrence Role of Pacing in Treatment of CSS CSS is a Class I indication for pacing (AHA and BPEG). Pacing therapy may be effective for CSS that is either Cardioinhibitory or Mixed cardioinhibitory/vasodepressor AV sequential pacing (DDD/DDI) is clearly preferable to ventricular demand (VVI) pacing. ____________________ Wagshal AB, Wang SKS. Carotid sinus hypersensitivity. In: Syncope: Mechanisms and management. Grubb BP, Olshansky B (eds). Armonk, NY: Futura, 1998. Brignole M, Menozzi C. Carotid sinus syndrome: Diagnosis, natural history and treatment. Eur J C P E. 1992;4: %6 (Mean follow-up = 6 months) Brignole et. Al. Diagnosis, natural history and treatment. Eur JCPE. 1992; 4:

Section VI: Insights into More Efficient and Effective Diagnosis and Treatment

Principal Causes of Orthostatic Syncope
Drug-induced (very common) diuretics vasodilators Primary autonomic failure multiple system atrophy Parkinsonism Secondary autonomic failure diabetes alcohol amyloid Alcohol orthostatic intolerance apart from neuropathy Orthostatic hypotension is an important cause of syncope. The medical history is usually sufficient to establish the diagnosis. However, defining the specific cause requires careful consideration of a number of important conditions. The most important conditions predisposing to orthostatic syncope are listed here.

Syncope Due to Arrhythmia or Structural CV Disease: General Rules
Often life-threatening and/or exposes patient to high risk of injury May be warning of critical CV disease Aortic stenosis, Myocardial ischemia, Pulmonary hypertension Assess culprit arrhythmia / structural abnormality aggressively Initiate treatment promptly Syncope occurring as a result of cardiac arrhythmias or in association with underlying structural heart disease requires careful and aggressive evaluation. Whereas syncope in patients with normal hearts is often relatively benign, syncope in the presence of cardiac disease is often indicative of a potentially life-threatening problem.

Principal Causes of Syncope due to Structural Cardiovascular Disease
Acute MI / Ischemia Acquired coronary artery disease Congenital coronary artery anomalies HOCM Acute aortic dissection Pericardial disease / tamponade Pulmonary embolus / pulmonary hypertension Valvular abnormalities Aortic stenosis, Atrial myxoma A list of important structural cardiovascular abnormalities to be considered during the diagnostic evaluation of syncope is provided. The list is not intended to be exhaustive of the possibilities, but provides some of the more commonly found conditions.

Syncope Due to Cardiac Arrhythmias
Bradyarrhythmias Sinus arrest, exit block High grade or acute complete AV block Tachyarrhythmias Atrial fibrillation / flutter with rapid ventricular rate (e.g. WPW syndrome) Paroxysmal SVT or VT Torsades de pointes Both excessively slow as well as excessively rapid heart rates may result in sufficient drop in systemic pressure to cause syncope. In the case of tachycardias, the syncope tends to occur at the onset of the episode, before vascular constriction has an opportunity to occur. Syncope may also occur at termination of tachyarrhythmias, if a prolonged pause occurs prior to resumption of a stable rhythm.

Rhythms During Recurrent Syncope
Bradycardia 36% Normal Sinus Rhythm 58% Normal Sinus Rhythm 58% Tachyarrhythmia 6% Krahn A, et al. Circulation. 1999; 99:

AECG: 74 yr Male, Syncope This ambulatory ECG (AECG) recording was obtained in a patient being evaluated for recurrent syncope. The finding of an abnormal sinus pause provides presumptive evidence suggesting a basis for the symptoms. However, this is not definitive evidence unless the patient has reproduction of his usual symptoms at the time. Further, the pathophysiologic basis for the pause (i.e., intrinsic disease vs. neurally-mediated origin (e.g., carotid sinus syndrome) cannot be determined definitively from this recording alone. From the files of DG Benditt, UM Cardiac Arrhythmia Center

Syncope: Torsades Torsades de pointes ventricular tachycardia often presents as syncope, although life-threatening sustained tachyarrhythmias may also occur. The underlying factors are most often either acquired or congenital long QT syndrome. In this case, the patient had been treated with quinidine for several weeks in an attempt to suppress episodes of atrial fibrillation. From the files of DG Benditt, UM Cardiac Arrhythmia Center

28 yo man in the ER multiple times after falls resulting in trauma
VT: ablated and medicated 83 yo woman Bradycardia: Pacemaker implanted Reveal® ILR recordings from patients with syncopal symptoms. The upper left recording was obtained in an 83 year old woman and suggests bradycardic episodes as a cause of syncope. The lower right recording was obtained in a younger patient with idiopathic ventricular tachycardia Reveal ® ILR recordings; Medtronic data on file.

Infra-His Block Syncope in this patient was due to intermittent AV block. This recording, obtained during EPS, reveals infra-His block. A pacemaker was implanted. From the files of DG Benditt, UM Cardiac Arrhythmia Center

Drug-Induced QT Prolongation
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 Nonsedating antihistamines (Terfenadine), Astemizole Others (Cisapride), Droperidol Numerous drugs have been associated with QT interval prolongation leading to susceptibility to torsade de pointes ventricular tachycardia. Certain of these agents have been removed from the market in the USA. These have been noted in parentheses.

Treatment of Syncope Due to Bradyarrhythmia
Class I indication for pacing using dual- chamber system wherever adequate atrial rhythm is available Ventricular pacing in atrial fibrillation with slow ventricular response The treatment of bradyarrhythmias associated with intrinsic conduction system disease resulting in syncope is usually cardiac pacing. On occasion, removal of an offending drug may be sufficient. The problem of neurally-mediated reflex bradyarrhythmias are dealt with separately.

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, ICD selected pts Atrial flutter – Ablation of reentrant circuit Ventricular Tachyarrhythmias; Ventricular tachycardia – ICD or ablation where appropriate Torsades de Pointes – withdraw offending Rx or ICD (long-QT/Brugada) Drug therapy may be an alternative in many cases This slide provides an overview of the multiple tachyarrhythmias that may cause syncope. EPS has proven more valuable in assessing tachyarrhythmia causes of syncope than those due to bradycardia.

Conclusion Syncope is a common symptom,
often with dramatic consequences, which deserves thorough investigation and appropriate treatment of its cause.

Disclaimer INDICATIONS 9526 Reveal® Plus Insertable Loop Recorder
The Reveal Plus Insertable Loop Recorder (ILR) is an implantable patient activated monitoring system that records subcutaneous ECG and is indicated for patients who experience transient symptoms that may suggest a cardiac arrhythmia. 9790 Programmer The Medtronic 9790 Programmers are portable, microprocessor based instruments used to program Medtronic implantable devices. 6191 Activator The Model 6191 Activator is intended for use in combination with a Medtronic Model 9525 Reveal® and the Model 9526 Reveal Plus Insertable Loop Recorders. CONTRAINDICATIONS There are no known contraindications for the implantation of the Reveal Plus ILR. However, the patient’s particular medical condition may dictate whether or not a subcutaneous, chronically implanted device can be tolerated. WARNINGS/PRECAUTIONS 9526 Reveal Plus Insertable Loop Recorder Patients with the Reveal Plus ILR should avoid sources of magnetic resonance imaging, diathermy, high sources of radiation, electrosurgical cautery, external defibrillation, lithotripsy, and radiofrequency ablation to avoid electrical reset of the device, and/or inappropriate sensing. Operation of the Model 6191 Activator near sources of electromagnetic interference, such as cellular phones, computer monitors, etc., may adversely affect the performance of this device. See the appropriate technical manual for detailed information regarding indications, contraindications, warnings, and precautions. Caution: Federal law (U.S.A.) restricts this device to sale by or on the order of a physician.

Disclaimer INDICATIONS Medtronic.Kappa 700 Series Pacemakers
The Medtronic.Kappa 700 Series pacemakers are indicated for rate adaptive pacing in patients who may benefit from increased pacing rates concurrent with increases in activity and are also indicated for dual chamber and atrial tracking modes in patients who may benefit from maintenance of AV synchrony. Dual chamber modes are specifically indicated for treatment of conduction disorders that require restoration of both rate and AV synchrony, which include various degrees of AV block to maintain the atrial contribution to cardiac output and VVI intolerance (e.g., pacemaker syndrome) in the presence of persistent sinus rhythm. 9790 Programmer The Medtronic 9790 Programmers are portable, microprocessor based instruments used to program Medtronic implantable devices. 9462 The Model 9462 Remote Assistant is intended for use in combination with a Medtronic implantable pacemaker with Remote Assistant diagnostic capabilities. CONTRAINDICATIONS The Medtronic.Kappa 700 Series pacemakers are contraindicated for the following applications: · Dual chamber atrial pacing in patients with chronic refractory atrial tachyarrhythmias. · Asynchronous pacing in the presence (or likelihood) of competitive paced and intrinsic rhythms. · Unipolar pacing for patients with an implanted cardioverter-defibrillator (ICD) because it may cause unwanted delivery or inhibition of ICD therapy. WARNINGS/PRECAUTIONS Medtronic.Kappa 700 Series patients should avoid sources of magnetic resonance imaging, diathermy, high sources of radiation, electrosurgical cautery, external defibrillation, lithotripsy, and radiofrequency ablation to avoid electrical reset of the device, inappropriate sensing and/or therapy. See the appropriate technical manual for detailed information regarding indications, contraindications, warnings, and precautions. Caution: Federal law (U.S.A.) restricts this device to sale by or on the order of a physician.

Additional Slides

Falls -- Incidence, Recurrence, CHS*
50% 1 30% 1 Percent of People 23% 2 CSS and Falls in the Elderly Falls are the leading cause of injury among the elderly. According to “Falling in the Elderly” (1995): 30% of the population older than 65 years of age falls each year. In the U.S., that amounts to about 9,000,000 people. 50% of these fallers have documented recurrence. 8% of the population greater than 70 years of age visit an ER for a fall. 40% of these visits result in hospitalization. Carotid sinus hypersensitivity and CSS increasingly are being recognized as attributable causes for unexplained falls and syncope in elderly patients. What is the contribution of CSS to these falls? This is an area of active research, but already-published results are suggestive: In one study, 279 fallers 50 years or older presenting to an emergency room with frequent or unexplained falls (at least 3 in previous 12 months) underwent carotid sinus massage, and 65 (23%) exhibited cardioinhibitory carotid sinus hypersensitivity (Richardson 1997). ____________________ Falling in the elderly: U.S. prevalence data. J Am Geriatr Soc, December, 1995. Richardson DA, Bexton RS, Shaw FE, et al. Prevalence of cardioinhibitory carotid sinus hypersensitivity in patients 50 years or over presenting to the accident and emergency department with “unexplained” or “recurrent” falls. PACE. 1997;(Pt II): Incidence > 65 yrs. old Recurrence CSH* present in fallers > 50 yrs. presenting at ER 1 Falling in the Elderly, 1995. 2 Richardson, PACE, 1997. * Carotid Sinus Hypersensitivity

VVS Pacing Trials Comparison Summary

Pacing in VVS Two randomized, controlled trials suggest benefit in selected patients with multiple (>5 lifetime) syncope recurrences and one or more of: prominent cardioinhibitory features asystolic pause >10 seconds sustained HR<40/minute The role of cardiac pacing in the treatment of VVS patients remains in evolution. However, to date 2 randomized controlled trials (RCTs) suggest that very symptomatic VVS patients may benefit from pacing. A third study (VPS2) has concluded, but the results are not yet made public

VVS Recurrences 35% of patients report syncope recurrence during follow-up ≤3 years Positive HUT with >6 lifetime syncope episodes: recurrence risk >50% over 2 years Recent studies suggest that VVS tends to recur in a substantial percentage of patients. Individuals who have historically experienced multiple syncopes over a long period of time are the ones at greatest risk of future recurrences. REFERENCE: Sheldon et al. Circulation 1996; 93: Savage et al. STROKE 1985; 16: Sheldon et al. Circulation 1996; 93: Savage et al. STROKE 1985; 16:

SAFE PACE 2: Syncope and Falls in the Elderly
30% of individuals >65 yrs fall each year 5% of falls result in fractures 1% of falls result in hip fractures SAFEPACE Pilot Study 18% prevalence of CSH in unexplained ‘fallers’ 31% in ‘fallers’ >80 yrs Recent findings from the SAFEPACE study suggest that Falls are an important source of morbidity in older patients. Further, it appears that many ‘fallers’ may have clinical findings suggestive of Carotid Sinus Syndrome. If these findings are corroborated, cardiac pacing may prove to be important for preventing syncope and falls in the elderly. REFERENCE Falling in the Elderly: U.S. Prevalence Data. Journal of the American Geriatric Society, December, 1995. Richardson DA, Bexton RS, Shaw FE, Kenny RA. Prevalence of cardioinhibitory carotid sinus hypersensitivity in patients 50 years or over presenting to the Accident and Emergency Department with “unexplained” or “recurrent” falls. PACE March 1997 (Part II):820-23 Kenny RA, J Am Coll Cardiol 2001; 38:

Rate Drop Response Overview
Detection Options Drop Detect Both Low Rate Detect Rate Drop Detection in Medtronic Kappa® Series Pacemakers Rate Drop Response therapy has evolved as clinical experience has been gained. In the Medtronic Kappa Generation pacing system three detection options are available: Drop Detect. The Drop Detect algorithm detects a relative heart rate drop of a pre-determined size. Low Rate Detect. The Low Rate Detect algorithm works like rate hysteresis but with more flexibility, intervening after the heart rate falls to a user-defined lower rate for a programmed number of beats. Both. With this option, either criterion will trigger intervention. The Low Rate Detection algorithm provides back-up detection. When a Rate Drop Detection therapy is programmed, an automatic diagnostic records summary data. A clinician selectable diagnostic also is available to record beat-to-beat data for one episode. Detects relative heart rate drops of a pre-determined size Detection occurs when either Drop Detection or Low Rate Detection criteria are met Detects heart rate that falls to a user-defined lower rate Rate Drop Detection in Medtronic Kappa® Series Pacemakers

Drop Detection with Intervention
Drop Detection Method: Drop Size 25, Drop Rate 70 110 100 Peak Rate=90 bpm 90 80 Drop Size=25 bpm Ventricular Rate Rate Drop Detection in Medtronic Kappa® Series Pacemakers Drop Detection allows the user to specify a relative drop in ventricular rate. Drop detection will only occur when two conditions are met: Drop Size: This is the size of the relative heart rate drop. Advance knowledge of the precise range of rates which will occur during a drop is not required to optimize the algorithm. To detect, the total ventricular rate drop must be greater than or equal to the user defined drop size. The “top” of the drop size is determined by the peak rate (defined on next slide) Drop Rate: Heart rate must be at or below this programmable rate for two consecutive beats for detection to occur. Fulfillment of these two criteria can occur in either order. In this slide, the heart rate has met the Drop Size and Drop Rate criteria and intervention has occurred. Note that in Medtronic Kappa®, 2 consecutive beats less than or equal to the Drop Size and Drop Rate triggers therapy. Two simplify programming, the number of “Confirmation Beats” is fixed at two based on prior physician experience. 70 Drop Rate 60 2 consecutive beats < Drop 50 Size and Drop Rate 40 Rate Drop Detection in Medtronic Kappa® Series Pacemakers

Drop Detect Peak Rate Drop Detection Method: Drop Size 25
120 Peak Rate=90 bpm 110 100 90 Ventricular Rate 80 Drop Size=25 bpm 70 Rate Drop Detection in Medtronic Kappa® Series Pacemakers Determination of Peak Rate In the Drop Detection detection algorithm, peak rate is determined as follows: The upper bound of the drop size is defined dynamically by the peak rate, which is the slower of two consecutive fastest beats during the detection window. This design avoids basing the peak rate on a PVC or a fast ventricular response to a PAC. The diagram shows an example. Following detection, intervention therapy is applied at a programmed rate for a programmed period of time. 60 50 40 Rate Drop Detection in Medtronic Kappa® Series Pacemakers

Low Rate Detect Low Rate Detection Method: Lower Rate 40, Detection beats 2 110 100 90 80 Ventricular Rate 70 Rate Drop Detection in Medtronic Kappa® Series Pacemakers The Low Rate Detection algorithm detects when the heart rate falls to a user-defined lower rate. It is important to note that the lower rate in the RDR Low Rate Detection method is the same as the pacemaker programmed lower rate. Low Rate Detection works as follows: The pacemaker intervenes when lower rate pacing occurs for a programmable number (1 to 3) of beats, as defined by the Detection Beats parameter. When Detection Beats = 2 or 3, intervention cannot be triggered by a single slow beat, such as a compensatory pause following a PVC. Intervention Rate and Duration are programmable, as with Drop Detection. This slide provides an example of Low Rate Detection and subsequent intervention. A cautionary note with the Low Rate Detection option: This method is contraindicated in patients who require low rate pacing support due to bradyarrhythmias. If patients do not require low rate pacing support, Low Rate Detection should be set below the lowest daily heart rate (<50ppm) in order to avoid inappropriate triggering of intervention pacing. 2 consecutive paced 60 beats at Lower Rate 50 40 Lower Rate 30 Rate Drop Detection in Medtronic Kappa® Series Pacemakers

Using Both Detection Algorithms
When both detection algorithms are used: Detection occurs when either Drop Detection or Low Rate Detection criteria are met Intervention Rate, Duration and Termination are programmed the same as when using the individual detection modes Rate Drop Detection in Medtronic Kappa® Series Pacemakers Rate Drop Detection with “Both” Option The “Both” option works exactly as you would expect it to work:. Intervention occurs when either Drop Detect or Low Rate Detect criteria are met. Each method operates independently. Drop Size and Drop Rate parameters are selected as for Drop Detect. Detection beats is programmed as for Low Rate Detect. Intervention Rate and Duration parameters apply for both detection modes. Intervention works the same as for either individual mode. Termination works the same as for either individual mode. Rate Drop Detection in Medtronic Kappa® Series Pacemakers

Rate Drop Intervention Therapy
DDD or DDI pacing Pacing intervention Paces at programmed Intervention Rate for programmed duration Pacing termination Pacing rate decreases until there are three consecutive atrial senses or Lower Rate is reached Rate Drop Detection in Medtronic Kappa® Series Pacemakers Intervention therapy is available in DDD and DDI modes. Pacing intervention starts at the programmed Intervention Rate and lasts for the programmed Duration. Intervention rates are programmable from bpm. Intervention pacing rates should be set as fast as possible without causing patient discomfort ( bpm), however, intervention should not be programmed less than 90 bpm. If patients are bothered by intervention pacing, this rate can be reduced somewhat. At the end of the Intervention Duration, the pacing rate decreases in steps until there are three consecutive atrial senses or the Lower Rate is reached. Rate Drop Detection in Medtronic Kappa® Series Pacemakers

Challenges of Syncope Cost Quality of Life Implications
Cost/year Cost/diagnosis Quality of Life Implications Work/financial Mobility (automobiles) Psychological Diagnosis & Treatment Diagnostic yield and repeatability of tests Frequency and clustering of events Difficulty in managing/treating/controlling future events Appropriate risk stratification Complex Etiology Syncope impacts patient quality of life, and health care costs in important ways. Establishing a precise diagnosis is often challenging due to the unpredictability of events and the limited positive predictive value of most available tests. The ‘gold standard’ remains the recording of the cardiac rhythm (and if possible the arterial pressure) during a spontaneous faint.

Diagnosing VVS Patient history and physical exam
Positive tilt table test (ACC Consensus Protocol) Overnight fast ECG Blood pressure Supine and upright Tilt to degrees Isoproterenol Re-tilt 60° - 80° 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 minutes. Tilt to degrees for 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): DG Benditt, Tilt Table Testing, 1996.

VVS: Treatment Overview
Education symptom recognition reassurance situation avoidance Tilt-Training prescribed upright posture Pharmacologic Agents salt/volume management beta-adrenergic blockers SSRIs vasoconstrictors (e.g., midodrine) Cardiac Pacemakers The treatment of recurrent VVS should focus primarily on education and salt/volume maintenance. Thereafter, physical maneuvers such as tilt-training are recommended. Pharmacologic and pacing treatment options remain for patients who continue to be symptomatic.

Tilt-Training: Clinical Outcomes
42 HUT positive (21±13 min) VVS patients Home training: two 30 minute sessions daily Outcomes 41/42 pts --->45 min asymptomatic HUT Clinical follow-up: 15.1±7.8 mos 36 pts syncope free 4 pts: presyncope 1 pt: syncope recurrences 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: .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: Reybrouck et al. PACE 2000; 23:493-8

Syncope A Diagnostic and Treatment Strategy

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