To pace or not to pace? Pacemakers for patients with neurocardiogenic syncope? Axel Brandes Consultant Cardiologist & Electrophysiologist Associate Professor of Cardiology Dept. of Cardiology – Arrhythmia Services Odense University Hospital, DK STARS Patients’ Day 2012, 23rd September 2012, Birmingham, UK Disclosures • Consulting fees/honoraria – AstraZeneca, Bayer, Biotronik, Boehringer-Ingelheim, Boston Scientific, Bristol-Myers Squibb, Medtronic, MSD, Pfizer, Sanofi, St. Jude Medical, Takeda-Nycomed • Research grants – Biotronik, Boehringer-Ingelheim, Medtronic, MSD, Sanofi, St. Jude Medical, Forest Research Inst. I have been fainting many times. Could a pacemaker help me? What are the treatment goals in neurocardiogenic syncope? • Prevention of recurrence • Prevention of associated injuries • Improvement of quality of life • Not to prolong survival, as this is a benign condition Case #1: History • 44 year old woman, sales assistent in a clothing shop, presenting at the syncope outpatient clinic • Several syncopes when she was a teenager, but no symptoms during many years (last episode about 20 years ago) • During the last 6 months she started again fainting • Her faintings often occur, when she is standing for a long time and there are many customers in the shop • Normally she has prodromal symptoms like sweating, nausea and restlessness, but the last episode occurred without any prodromes. She stood at the counter, then fainted suddenly and hit her head in a clothing rack. A colleague told her later, that she had lost consciousness for about 3 minutes. • Her colleagues call 999. Upon arrival of the ambulance she is awake and fully conscious. Case #1 (cont’d) • A + E department – Upon arrival she feels a little tired, but otherwise well-being, awake, and fully conscious. – BP 115/70, O2-saturation 95% without oxygen supply. – 12-lead ECG: normal sinus rhythm, heart rate 69 bpm. – A gash in her forehead is sutured. – Discharge after 3 hours’ observation, where she well-being. – Referral to syncope outpatient clinic. Case #1 (cont’d) • Syncope outpatient clinic – History is confirmed. She has syncopes with and without prodromal symptoms – BP 120/73 (supine), 115/67 (upright) – Normal carotid sinus massage – Normal echocardiography – 72-hours Holter monitoring • Normal sinus rhythm, few PAC’s – Set to tilt table test Case #1 (cont’d) • Tilt table test – After 4.5 minutes standing • Nausea, dizziness, then rapid loss of consciousness • 29 sec. asystole accompanied by fall of BP – Cardioinhibitory VVS ECG Syncope tilt down Asystole 29 s Tilt-up procedure Heart rate Syncope Supine Dizzy No symptoms tilt down RR = 825 ms BPsys = 118 mmHg Systolic BP Warning time 9 s. Diastolic BP 2 ss 30 Positive tilt table test with Standing Supine cardioinhibitory response 4.5 min What to do now? 1) Talk with the patient to reassure her? 2) Start midodrine? 3) Fit a pacemaker? Case #1 (cont’d) • Longer information talk with the patient and joint decision to fit a pacemaker • Dual chamber pacemaker ten days later • Since the patient is doing well without any syncopes Case #2 • 59 year old woman with vasovagal disease since 2007 and several syncopes a week • Very extensive cardiac and neurologic evaluation at a collaborating hospital • Implantable loop recorder fitted → single episode of 3rd degree AV block • Implantation of a dual chamber pacemaker, but continues to faint many times a week Referred to outpatient syncope clinic at OUH Case #2 (cont’d) • Medication at 1st visit at syncope clinic – Metoprolol 100 mg b.i.d. – Sertraline 50 mg s.i.d. • Treatment changes – – – – Stop metoprolol Start midodrine Prescribe elastic stockings Recommended to increase her salt intake • But continues to faint Case #2 (cont’d) • December 2011 box change (dual chamber pacemaker with closed loop stimulation) • Reduction of syncopal episodes from several times a week to several times a month • May 2012 again increase in number of syncopal episodes with several episodes daily • Dose increase to midodrine 15 mg t.i.d. • Continues to have several syncopes a month, exacerbation often occurs due to physical and mental stress. Patient now seeks early retirement. Why does pacing work in some patients with neurocardiogenic syncope, but not in all? Classification of syncope according to etiology vs. mechanism Tilt table test Cardioinhibitory component Mixed Vasodepressor component Modif. Brignole M and Hamdan MH. J Am Coll Cardiol 2012;59:1583-91 How can we identify patients with neurocardiogenic syncope, who might benefit from pacemaker implantation? Diagnostic tests to select patients with neurocardiogenic syncope for pacing • Tilt table test • Monitoring – Holter monitoring – External loop recorder – Implantable loop recorder Randomized trials of pacing in patients with neurocardiogenic syncope Sud S, et al. Am J Med 2007;120:54-62 Effect of pacing on recurrence of syncope in randomized trials Patients with cardioinhibitory response to tilt table testing only Sud S, et al. Am J Med 2007;120:54-62 Estimation of the expectation response of cardiac pacing in preventing recurrent syncope Sud S, et al. Am J Med 2007;120:54-62 Tilt table test for the diagnosis and management of neurocardiogenic syncope • The positive response rate is only 61 – 69% • A cardioinhibitory response to tilt table testing predicts with high probability an asystolic spontaneous syncope • A vasodepressor, a mixed or a negative response does not exclude asystole during spontaneous syncope How can we better identify patients with neurocardiogenic syncope, who might benefit from pacemaker implantation? Heart monitoring options Syncope occurs infrequently, long-term monitoring is likely to be most effective 12-Lead 10 Seconds Holter Monitor 3 Days (up to 7 days) Typical Event Recorder 7 Days MCOT External Loop Recorder ILR ILR = implantatble loop recorder MCOT= mobile cardiac outpatient telemetry 30+ Days 36 Months Implantable Loop Recorders (ILR) Reveal® system, Medtronic Inc., Minneapolis, MN -manual/auto trigger -remote download (CareLink®) Sleuth®, Transoma Inc., St Paul, MN -manual/auto trigger -wireless data transmission Confirm®, St Jude Medical St Paul, MN -manual/auto trigger -remote download ISSUE-2 Study Multi-centre, prospective, observational study Inclusion criteria • ≥ 3 syncopes during last 2 years • Severe clinical presentation • Suspected or definite neurallymediated syncope after initial evaluation (history, physical exam, 12-lead ECG, supine/upright BP, CSM, HUT, ATP test) • Age >30 years ISSUE-2 Study Recurrence of syncope of patients with documented asystole/bradycardia and PM compared with patients without asystole/bradycardia Brignole M, et al. Eur Heart J 2006;27:1085-92 ISSUE-2 Study Poor correlation between TT response and the mechanism of syncope as documented by ILR (n = 38) Brignole M, et al. Eur Heart J 2006;27:2232-9 The clinical impact of implantable loop recorders in patients with syncope – the EaSyAS I Trial Farwell DJ & Sulke N. Int J Cardiol 2005;105:241-9 Pacemaker therapy in patients with neurally mediated syncope and documented asystole – The ISSUE-3 Trial Inclusion criteria •Suspected or certain NMS, based on the guidelines •3 syncope episodes in the last 2 years •Clinical presentation of syncope of sufficient severity requiring treatment initiation in the physician’s and the patient’s judgement (very frequent, e.g. alters the quality of life, recurrent and unpredictable, ‘high risk’ of trauma, during ‘high risk’ activity) •Age >40 years •Negative carotid sinus massage •Patient’s accept to have an ILR implantation Brignole M, et al. Circulation 2012;125:2566-71 ISSUE-3 Steering Committee. Europace 2007;9:25-30 Time to first recurrence of syncope – The ISSUE-3 Trial Brignole M, et al. Circulation 2012;125:2566-71 Care pathway for syncope patients with normal ECG, no structural heart disease, where neurocardiogenic syncope is suspected Clinical criteria •Age >40 years •Frequent (>5) episodes •No prodromal symptoms •Major risk of injury •Syncope during high risk activity •Alternative therapy failed No Other treatment options (physical manoeuvres) No ILR-guided therapy (as necessary) Yes Tilt table test: Asystole (VASIS 2B) Yes DDD pacemaker CLS/Rate-drop response Brignole M, ESC E-Journal 5, no. 39 Implantable loop recorder (ILR): What do guidelines tell us? Guidelines for the diagnosis and management of syncope (version 2009) • ILR is indicated in an early phase of evaluation in patients with recurrent syncope of uncertain origin, absence of high risk criteria and a high likelihood of recurrence within battery longevity of the device IB • ILR is indicated in high risk patients in whom a comprehensive evaluation did not demonstrate a cause of syncope or lead to a specific treatment IB • ILR should be considered to assess the contribution of bradycardia before embarking on cardiac pacing in patients with suspected or certain reflex syncope presenting with frequent or traumatic syncopal episodes IIaB • External loop recorders should be considered in patients who have an inter-symptom interval ≤4 weeks IIaB Moya A, et al. Eur Heart J 2009;30:2631-2671 Suspected neurally mediated cause Vasovagal syncope suspected Is the person 60 years or older? Carotid sinus syncope suspected Yes Do not offer a tilt test to people who have a diagnosis of vasovagal syncope on initial assessment • Offer carotid sinus massage • Carry out this test in a controlled environment, with ECG recording and resuscitation equipment available Only consider a tilt test if the person has recurrent episodes of TLoC that adversely affect their quality of life, or represent a high risk of injury, to assess whether the syncope is accompanied by a severe cardioinhibitory response (usually asystole) No • Offer an ambulatory ECG – choose type of ambulatory ECG based on person’s history (and in particular, frequency) of TLoC (see box 8) • Do not offer a tilt test before the ambulatory ECG Syncope due to marked bradycardia/asystole and/or marked hypotension reproduced? Yes Click here to return to slide 9 (specialist cardiovascular assessment and diagnosis) Unexplained cause Diagnose carotid sinus syncope NICE Clinical Guideline 109, August 2010 at http://www.nice.org.uk No Negative carotid sinus massage test (includes carotid sinus massage induction of asymptomatic transient bradycardia or hypotension) 11 Pacing: What do guidelines tell us? Guidelines for the diagnosis and management of syncope (version 2009) • Cardiac pacing should be considered in patients with frequent recurrent reflex syncope, age >40 years, and documented spontaneous cardioinhibitory response during monitoring IIaB • Cardiac pacing may be indicated in patients with tiltinduced cardioinhibitory response with recurrent frequent unpredictable syncope and age >40 after alternative therapy has failed IIbC • Cardiac pacing is not indicated in the absence of a documented cardioinhibitory response IIIA Moya A, et al. Eur Heart J 2009;30:2631-2671 Conclusions • Pacing in patients with neurocardiogenic syncope is still a difficult case • Treatment success is dependent on the underlying mechanism of neurocardiogenic syncope • Use of an implantable loop recorder can improve identification of patients with neurocardiogenic syncope, in whom pacemaker treatment is helpful, esp. those with spontaneous asystolic episodes • Do not expect miracles • You might need a combination therapy • Discuss with your heart rhythm specialist, as benefit of pacemaker treatment has to be balanced with potential side effects