Tilt asistolico VASIS 2B Pro

Transcription

1 Tilt asistolico VASIS 2B Pro Francesco Arabia U.O. Cardiologia UTIC Emodinamica e Cardiologia Interventistica Presidio Ospedaliero A. Pugliese Catanzaro

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4 Vasis 1992 Vasis 2000 Tipo 2A : 'la frequenza cardiaca scende a meno di 40 bpm per più di 10 s o si verifica asistolia per più di 3 s; la pressione arteriosa scende prima della frequenza cardiaca Tpo 2B: la frequenza cardiaca scende a meno di 40 bpm per più di 10 s o si verifica asistolia per più di 3 s; la caduta della pressione arteriosa coincide con la caduta della frequenza cardiaca Tipo 2 A, cardioinibitoria senza asistolia:'la frequenza cardiaca scende a meno di 40 bpm per più di 10 s, ma non si verifica asistolia maggiore di 3 secondi. La pressione cala prima della diminuzione della frequenza cardiaca. Tipo 2 B, cardioinibitoria con asistolia: Si verifica asistolia maggiore di 3 secondi. Il calo pressorio coincide con la diminuzione della frequenza cardiaca o la precede SuJon R, Petersen M, Brignole M, Raviele A, Menozzi C, Giani P. Proposed classificapon for Plt induced vasovagal syncope. Eur J Cardiac Pacing Electrophysiol 1992; 2: M. Brignole, C. Menozzi,A. Del Rosso, S. Costa, G. Gaggioli, N. BoJoni,P. Bartoli and R. SuJonNew classificapon of haemodynamics of vasovagal syncope: beyond the VASIS classificapon Europace (2000) 2, 66 76

5 M. Brignole, C. Menozzi,A. Del Rosso, S. Costa, G. Gaggioli, N. BoJoni,P. Bartoli and R. SuJonNew classificapon of haemodynamics of vasovagal syncope: beyond the VASIS classificapon Europace (2000) 2, 66 76

6 The Role of Pacing as Therapy for VVS VVS with +HUT and cardioinhibitory response: Class IIb indication for pacing Three randomized, prospective trials reported benefits of pacing in select VVS patients: VPS I Open label VASIS SYDIT Subsequent study results less clear: 1Connolly SJ. J Am Coll Cardiol. 1999;33: Sutton R. Circulation. 2000;102: Ammirati F. Circ. 2001;104: Double blind VPS II Synpace 4Connolly 5Giada 6Occhetta E, et al. Europace. 2004;6:

7 VPS I North American Vasovagal Pacemaker Study Objective: To evaluate pacemaker therapy for severe recurrent vasovagal syncope Randomized, prospective, single centre N=54 patients 27: DDD pacemaker with rate drop response 27: No pacemaker Inclusion: Vasodepressor response! 6 syncopal events ever! +HUT! RelaPve bradycardia Primary outcome: First recurrence of syncope Connolly SJ. J Am Coll Cardiol. 1999;33:16-20.

8 VPS I North American Vasovagal Pacemaker Study Cumulative Risk (%) No Pacemaker (PM) 2P= Pacemaker Time in Months 6 (22%) with PM had recurrence vs. 19 (70%) without PM 84% RRR (2p= ) Connolly SJ. J Am Coll Cardiol. 1999;33:16-20.

9 VASIS Vasovagal Syncope International Study Objective: To evaluate pacemaker therapy for severe cardioinhibitory tilt-positive neurally mediated syncope Randomized, prospective, multi-centre N=42 patients 19: DDI pacemaker (80 bpm) with rate hysteresis (45 bpm) 23: No pacemaker Inclusion: Positive cardioinhibitory response! > 3 syncopal events in 2 years and last event occurring within 6 months of enrollment and,! PosiPve VASIS type 2A or 2B cardioinhibitory response to HUT and,! Age > 40 years or drug refractory if < 40 years Primary outcome: First recurrence of syncopeope Sutton R. Circulation. 2000;102:

10 VASIS VAsovagal Syncope International Study 100 Pacemaker (PM) % Syncope-Free p= No Pacemaker 20 Sutton R. Circulation. 2000;102: Years Results: 1 (5%) with PM had recurrence vs. 14 (61%) without PM 2-year estimated syncope recurrence rate was 6% Sutton R. Circulation. 2000;102:

11 SYDIT Syncope Diagnosis and Treatment Objective: To compare the effects of cardiac pacing with pharmacological therapy in patients with recurrent vasovagal syncope Randomized, prospective, multi-centre N=93 patients 46: DDD pacemaker with rate drop response 47: Atenolol 100 mg/die > 55 yrs Inclusion: Positive HUT with > 3 syncopal relative episodes bradycardia in 2 years Primary outcome: First recurrence of syncopee Ammirati F. Circulation. 2001;104:52-57.

12 1.0 SYDIT Syncope Diagnosis and Treatment Pacemaker (PM) % Syncope-Free p= Drug Time (Days) 2 (4%) with PM had syncope recurrence vs. 12 (26%) without PM 2-year estimated syncope recurrence rate was 7,2% Ammirati F. Circulation. 2001;104:52-57.

13 VPS II Vasovagal Pacemaker Study II Objective: To determine if pacing therapy reduces the risk of syncope in patients with vasovagal syncope Randomized, double-blind, prospective, multi-centre N=100 patients 52: Only sensing without pacing 48: DDD pacemaker with rate drop response Inclusion: Positive HUT with (HRxBP) < 6000/min x mmhg! 6 syncope events ever or! > 3 syncope events in 2 years or! > 1 syncope event in 6 months Primary outcome: First recurrence of syncope Connolly S. JAMA. 2003;289:

14 1.0 VPS II Vasovagal Pacemaker Study II 0.8 Cumulative Risk Only Sensing Without Pacing (ODO) 0.2 Dual Chamber Pacing (DDD) Months Since Randomization Results: 33% recurrence with pacing vs. 42% with only sensing (p=ns) Connolly S. JAMA. 2003;289:

15 SYNPACE Vasovagal Syncope and Pacing Objective: To determine if pacing therapy will reduce syncope relapses in patients with recurrent vasovagal syncope, compared with those having a pacemaker programmed OFF Randomized, double-blind, prospective, multi-centre, placebo-controlled N=29 patients 16: DDD PM with rate drop response programmed ON 13: PM programmed OFF (OOO mode) Inclusion: Recurrent VVS and +HUT with asystolic or mixed response Primary outcome: First recurrence of syncope Raviele A.. Europace. 2001;3: Raviele A, et al. Eur Heart J. 2004;25:

16 % Syncope-Free SYNPACE Vasovagal Syncope and Pacing p=0.58 Recurrent VVS and +HUT with asystolic or mixed Pacemaker OFF response 2A+2B Age : 53 Pacemaker ON Raviele A, et al. Eur Heart J. 2004;25: Days Since Randomization 50% recurrence with pacing ON vs. 38% with pacing OFF (p=ns)

17 Context and Background: THE EFFICACY OF CARDIAC PACING FOR PREVENTION OF SYNCOPAL RECURRENCES IN PATIENTS WITH NEURALLY MEDIATED SYNCOPE Multicenter, randomized studies with results in favour of pacing (open-label) - - SYDIT. Circulation year estimated syncope recurrence rate was 7,2% VASIS. JAMA year estimated syncope recurrence rate was 6% - SYDIT Circulation 2001 ISSUE 2 Randomized double-blind controlled trials failed to prove superiority of cardiac pacing over placebo VPS II trial. JAMA months syncope recurrence rate was 31% SYNPACE trial. Eur Heart J year syncope recurrence rate was 29%

18 Eligible 442 Implanted ILR 417 Started Phase I FU 392 Syncopal recurrence 143 ECG-documented syncope No ILR implant 25 No follow-up 15 Drop-out ISSUE 2 Asystole, # 57 Bradycardia, # 4 No or slight rhythm variations # 29 Progressive sinus tachycardia #7 Tachyarrhythmia, # 9 Started Phase II No follow-up 53 ILR-based specific Rx: Pacemaker #47 Defibrillator #1 Catheter ablation #4 Antiarrhythmic drug #1 50 Non- specific Rx

19 ISSUE 2 1-year estimated syncope recurrence rate was 5% ( burden 0,05 ±0,15) " Pacing potentially effective in patients with documented asystole " The mechanism of spontaneus NMS documentated by ILR ISSUE-2 was not a formal controlled double-blind trial was riproducible " Asystolic NMS treated with pacemaker showed a > 80% relative Studio risk reduction mulpcentrico of syncopal recurrence prospebco osservazionale Eur Heart J 2006; 27,

20 Europace Jan;9(1):31-3. Pacing for neurally mediated syncope: is placebo powerless? Brignole M, SuJon R. CONCLUSIONS: Placebo is not an effecpve therapy for neurally mediated syncope. Different selecpon criteria in papents who are candidates for cardiac pacing- for example, presence, absence, or severity of the cardioinhibitory reflex may separate posipve from negapve trials.

21 ISSUE 3" SYNCOPE" ISSUE 3 International Study on Syncope of Uncertain Etiology 3 Pacemaker therapy for papents with neurally- mediated syncope and documented asystole A randomized controlled double- blind trial Objective: to determine if pacing therapy reduces recurrences in patients with severe documented spontaneous asystolic NMS

22 ISSUE 3" ISSUE 3 International Study on Syncope of Uncertain Etiology 3 SYNCOPE" Total 29 centers

23 Background: ISSUE 3 International Study on Syncope of Uncertain Etiology 3 Two RCTs* failed to prove superiority of cardiac pacing over placebo of unselected NMS papents with posipve Plt tespng Study hypothesis: Pacing therapy is effecpve for prevenpng syncope recurrence in papents with NMS and documented asystole * VPS II trial. JAMA 2003; 289: Synpace trial. Eur Heart J 2004: 25:

24 Screening phase 511 met inclusion criteria and received an ILR SYNCOPE" ISSUE 3" Study phase 89 had ECG documentapon of: - syncopal recurrence with asystole of 12±10 s (#72) or - non- syncopal asystole of 10±6 s (#17) 77 randomized 12 refused randomizapon 38 assigned and received Pm ON 39 assigned and received Pm OFF 3 lost to follow- up 8 had Pm reprogrammed DDD/VVI in absence of primary end- point 9 followed- up (registry): 6 implanted Pm 3 no therapy 38 analysed 39 analysed 9 analysed

25 SYNCOPE" ISSUE 3" ILR screening phase: documented events Tachycardia Tachicardia 10% Normal Normal SR SR Asystole (11 ± 4 s) Bradycardia Total end- points: 158

26 ISSUE 3" ISSUE 3 populapon SYNCOPE" Features: Mean age at presentapon: >60 years History of recurrent syncopes beginning in middle or older age Severe clinical presentapon requiring treatment (high risk and/or high frequency) Atypical presentapon without warning Frequent injuries related to presentapon without warning ILR documentapon of long pauses (mean 11 seconds) EsDmated prevalence: 9% of papents affected by NMS referred to Syncope Clinic

27 ISSUE 3" SYNCOPE" Freedom from syncopal recurrence Number at risk Pm OFF Pm ON First syncope recurrence (intendon- to- treat) Kaplan-Meier survival estimates 25% 37% log rank: p=0.039 RRR at 2 yrs: 57% 25% 57% Months Pm ON Pm OFF

28 ISSUE 3" ISSUE 3 International Study on Syncope of Uncertain Etiology 3 SYNCOPE" Conclusions Dual- chamber permanent pacing is effecpve in reducing recurrence of syncope in papents 40 years with severe asystolic NMS. The observed 32% absolute and 57% relapve syncope reducpon rate support the use of this invasive treatment for the relapvely benign NMS. The overall strategy of using an ILR in order to determine indicapon for pacing likely contributed to the posipve findings and explains the discrepancy with the negapve results of some previous report.

29 According to the ILR findings, the accuracy of the diagnosis of NMS made on inipal evaluapon was 87%. The diagnospc accuracy of Plt table test was low: TT was posipve in 56% NMS, 43% non- NMS; an asystolic response was present in 21% NMS and 0% non- NMS Heart 2013;99: doi: /heartjnl

30 ON-TREATMENT ANALYSIS The recurrence of syncope occurred in 10 paced patients (17%) 40 non-paced patients (46%). At 21 months, the estimated product-limit syncope recurrence rates were 27% and 54% respectevely. Risk of recurrence with cardiac pacing was reduced by 57%

31 -Positive TTT is more likely correlated with a higher frequency of recurrences of syncope in the group treated using a PM, while a negative response seems to predict the success of the pacing therapy. -The results of our study show the capacity of TTT to identify patients with a possible concomitant vasodepressive form (!?!? ) Consequently PM is not sufficient in a group of patients with positive TTT response. Circ Arrhythm Electrophysiol Feb;7(1):10-6

32 Physical counter- pressure manoeuvres in prevendng syncopal recurrence in padents older than 40 years with recurrent neurally mediated syncope: a controlled study from the Third InternaDonal Study on Syncope of Uncertain EDology (ISSUE- 3) Marco Tomaino, CrisDna Romeo, Elena Vitale, Teresa Kus, Angel Moya, Nynke van Dijk, Silvia Giuli, Giorgia D'Ippolito, Alessandra GenDli, Richard Suaon, DOI: hap://dx.doi.org/ /europace/euu First published online: 6 June 2014 Issue-3 population: - OLDER PATIENTS - ABSENCE OF PRODROME At 21 months, the estimated product-limit syncope recurrence rates were 42% (95% CI 29-62) and 64% (95% CI respectively (p=0.30)

33 Bolzano ISSUE 3 TRIAL SYNCOPE TAKE HOME MESSAGES " Clinical evaluation " Diagnostic iter guided by ILR " Selection of patients who undergo to PM implantation " Reducing of recurrences and improvement of QOL by pacing DDD RDR " PCM Therapy

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35 SUP 2

36 SUP 2 The recurrence rate was similar in the 65 CSM+ (11%), 32 TT+ (7%) and 23 ILR+ (7%) patients. The actuarial total syncope recurrence rate was : recurrence rate was 9% 9% (95% CI 6-12 at 1 years and 15% (95% CI, 10-20) at two years and when significantly lower than that observed in the control group of 124 patients with unspleined syncope who did not receive pacemaker i.e. 22% (95% CI, ai 1 year and 37% (95%, CI 30-43) at 2 years ( p=0,004)

37 SUP 2 Asystolic Tilt Test and PM. About half of older patients with severe recurrent syncopes without prodromes have an asystolic reflex for which cardiac pacing is effective in preventing syncopal recurrences. The recurrence rate is low irrespective of the index diagnostic test

38 Syncope Unit CZ Aevità Totale 1610 pz Lineare (2008) Lineare (2009) Lineare (2010) Lineare (2011) Lineare (2012) Lineare (2014)

39 ; 61% RISULTATI 39% % % 110; 7% 71; 5% 133; 8% 57; 5% NegaPvi Tipo I Tipo 2A Tipo 2B Tipo 3 MSC pos

40 RISULTATI ; 30% 110; 19% 133; 22% % % 71; 12% ; 3% 20 0 Tipo I Tipo 2A Tipo 2B Tipo 3 MSC pos Altri

41 PazienP con risposta Ppo 2B PZ % 33% 4% 10% 6 mesi 12 mesi 18 mesi 24 mesi TraJaP con PM No PM 48 pz età media 68 aa Pz DDD PM rate drop response 60 pz 3 età media 30 aa Misure comportamentali

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43 DISTRIBUZIONE PER FASCE DI ETA Donne Uomini >70