Ο απινιδωτής, σε ασθενή με δομική καρδιοπάθεια, ενεργοποιείται συχνά. Τι θα κάνω;

Ο απινιδωτής, σε ασθενή με δομική καρδιοπάθεια, ενεργοποιείται συχνά. Τι θα κάνω; Παναγιώτης Ιωαννίδης Διευθυντής Τμήματος Αρρυθμιών & Επεμβατικής Ηλεκτροφυσιολογίας Βιοκλινικής Αθηνών Σεμινάρια Ομάδων Εργασίας 2017 Θεσσαλονίκη, 16/2/2017

Disclosures Speaker s and consulting honoraria, proctoring, travel support St Jude Medical Medtronic Pfizer

Mortality Rate Reduction With ICDs Primary Prevention Secondary Prevention 80% 60% 40% 20% 75% 76% 54% 55% 61% 31% 23% 60% 40% 20% 56% 59% 31% 28% 33% 20% 0% MADIT I MUSTT MADIT II SCD-HeFT 0% AVID CASH CIDS Overall Death Arrhythmic Death Overall Death Arrhythmic Death ICD mortality reduction in primary prevention trials are equal or greater than those in secondary prevention trials

ICD Therapy: A powerful tool to reduce mortality 40 35 30 25 20 15 10 5 0 Number Needed to Treat (NNT) to Save a Life 3 4 ICD Therapy 11 9 18 MUSTT MADIT I MADIT II AVID SCD-HeFT SAVE Merit-HF 4S Amiodarone Meta Analysis 20 Captopril Drug Therapy 5Yr 2.4Yr 3Yr 3Yr 3.8Yr 3.5Yr 1Yr 6Yr 2Yr 26 Metoprolol 28 Simvastatin 37 Amiodarone NNT= 100 / %mortality in control group - %mortality in treatment group

The patient with ICD shocks: A daily clinical issue

3-fold increase in panic disorders and agoraphobia in patients with 2 ICD shocks annually Godemann et al. Clin. Cardiol. 2004;27:321-326

ICD shocks may have a negative impact on patients' quality of life ICD shocks are associated with higher mortality ICD shocks may be a marker of more advanced heart disease, direct damage to the heart from these shocks could increase mortality Thus, it is important to identify therapies that can effectively reduce the risk of ICD shocks.

MADIT II Sub-analysis: Episodes of VT/VF predict increased mortality and HF despite ICD therapy Patients who received appropriate ICD shocks have 3.5 fold higher risk of death relative to patients who did not receive appropriate therapy Moss et al. Circulation 2004;110:3760-65

Defibrillator Shocks in SCD-HeFT Poole et al. NEJM 2008;359:1009-17

Shocks after VT/VF contribute to intracellular Ca ++ overload and maintain a vicious cycle of arrhythmia promotion and electrical storm Tsuji et al. Circulation 2011;123:2192-2203 Tsuji Y. Journal of Electrocardiology 2011;44:725-729

MADIT-RIT 1500 pts with a primary-prevention indication for ICD with 1/3 programming configurations 1,4 years follow-up Moss et al NEJM 2012;367:2275-83

MADIT-RIT Moss et al NEJM 2012;367:2275-83

1,670 primary prevention ICD patients Randomized n=846 +longer detection intervals n=824 Less ICD shocks More inappropriate / same appropriate shocks in control group Reduction in all-cause mortality in the less shock group 4/846 (0.47%) more arrhythmic syncopal episodes Saeed et al. J Cardiovasc Electrophysiol 2014;25:52-59

The yin and the yang in ICD therapy

Electrical Storm: Definition, Incidence Definition Electrical storm is best defined as the occurrence of 3 or more distinct episodes of VT and/or VF within a 24-h period, either resulting in a device intervention or monitored as a sustained VT ( 30sec). Some authors have set an arbitrary 5 min interval between VT/VF episodes to define electrical storm Incidence Israel CW & Barold S. Ann Noninvasive Electrocardiol 2007;12:375-82 According to the commonly accepted definition of electrical storm, incidence is about 10% to 20% in patients who have an ICD for secondary prevention of sudden cardiac death. Exner et al. Circulation. 2001;103:2066-71 Nademanee et al. Circulation. 2000;102:742-7 Bänsch et al. JACC 2000;36:566-73 The incidence is lower when ICDs are placed for primary prevention Moss et al. NEJM 2002;346:877-83

Prognosis of Electrical Storm Effect of electrical storm on all-cause mortality Guerra F et al. Europace 2014;16:347-53

Management of Multiple ICD Shocks / Electrical Storm Is there a reversible cause? Whenever a reversible cause can be identified measures should be undertaken for its rapid correction Triggers of Electrical Storm Acute coronary event Electrolyte disturbance Exacerbation of heart failure Braunschweig F et al. Europace 2010;12:1673-90 <20% of events (lower for VT as compared to VF) Severe ischemia Adjustment or non compliance to AAD Rx Unusual psychological stress Israel CW & Barold S. Ann Noninvasive Electrocardiol 2007;12:375-82

Arrhythmic Syncope Before Defibrillation 70-year-old man Old anterior MI, LVEF=35% CAD 3 vessel disease CABG with 3 vein grafts ICD (2012) for primary prevention (PVCs, Inducible VT) Angina in minimal effort Electrical storm with syncope Cycle Length ~220ms: VF Athens Bioclinic EP Department

Arrhythmic Syncope Before Defibrillation 70-year-old man Old anterior MI, LVEF=35% CAD 3 vessel disease CABG with 3 vein grafts ICD (2012) for primary prevention (PVCs, Inducible VT) Angina in minimal effort Electrical storm with syncope Detection Charging 1) Reprogramming: from 18/24 to 9/12 VT/VF Detection Cycle Length ~220ms: VF Charging Shock Athens Bioclinic EP Department

Arrhythmic Syncope Before Defibrillation 70-year-old man Old anterior MI, LVEF=35% CAD 3 vessel disease CABG with 3 vein grafts ICD (2012) for primary prevention (PVCs, Inducible VT) Angina in minimal effort Electrical storm with syncope Detection Charging 1) Reprogramming: from 18/24 to 9/12 VT/VF Detection 2) Revascularization Cycle Length ~220ms: VF Charging Shock Athens Bioclinic EP Department

Acute Management of The Electrical Storm Respiratory and circulatory assistance if necessary Sedation Monomorphic VT Polymorphic VT /VF Beta-blockers Class III AADs Drugs ICD reprograming Ablation Ischemic Heart Beta-blockers Amiodarone Revascularization Ablation With QT prolongation Discontinue offending drugs Magnesium Pacing With Heart Failure Beta-blockers Amiodarone Heart failure treatment Ablation

Cumulative Rate of Shock for the 3 Treatment Groups by Time Since Randomization β-blocker Sotalol Amiodarone + β-blocker Connolly et al. JAMA 2006;295:165-171

Cumulative Rate of Shock for the 3 Treatment Groups by Time Since Randomization β-blocker Sotalol Amiodarone + β-blocker Discontinuation at 1 year: 5.3% for blocker alone 18.2% for amiodarone, 23.5% for sotalol Connolly et al. JAMA 2006;295:165-171

When amiodarone fails to control VT Again Amiodarone Re-loading dose up to 1200mg/daily for up to 2 weeks followed by 400 mg/day for 1 week, and 200-300 mg/day thereafter Mexiletine Its mechanism of action differs significantly from the predominant effects of amiodarone, Ranolazine Dofetilide Azimilide Dorian et al. JACC 2008;52(13):1076-83

IB class anti-arrhythmics: Block Na channels and shorten repolarization Mexiletine when added to amiodarone in case of amiodarone inefficacy, reduces VT/VF events and appropriate ICD therapies Gao et al J Cardiovasc Pharmacol 2013;62:199-204

Dose of Ranolazine 500-1000mg twice daily Bunch et al PACE 2011;34:1600-1606

Antiarrhythmic Drugs: Possible consequences Conduction slowing Conduction Velocity S = V X t Excitable Gap increment Higher probability for VT induction Need for ventricular pacing Re-entrant Circuit Diameter (constant) Conduction Time

Catheter Ablation: A useful tool to reduce the arrhythmic burden

Long-Term Outcome of pts with Electrical Storm after Catheter Ablation Catheter Ablation Effect Class A: Non-inducibility (72%) Class B: inducibility of 1 nonclinical VT (18%) Class C: inducibility of clinical VT (11%) Median follow-up of 22 months 92% free of ES recurrence 66% free of VT recurrence Carbucicchio et al. Circulation 2008;117:462-469

Results of Catheter Ablation Patients,n EF (%) Substrate Treatment Type of VT Mapping Prospective randomized multicentre trials Acute success,n (%) FU (ms) Long-term success Long-term mortality Kuck et al. 2010 9 107 ICM VT ablation + ICD vs. ICD only Only stable VT Mapping during VT/substrate mapping 22.5 (9) Active 52 34 ± 10 27 (60%) 47% 10% a Control 55 34 ± 9 29% 7% a Reddy et al. 2007 10 128 ICM VT ablation + ICD vs. ICD only All VT Substrate mapping 22.5 (5.5) Active 64 31 ± 10 NA b 88% 9% Control 64 33 ± 9 67% 17% P = 0.29 Non-randomized prospective multicentre trials Tanner 2009 63 30 ± 13 ICM VT ablation All VT Stevensonet al. 2008 11 231 25 d ICM VT ablation All VT Calkins et al. 2000 7 146 31 ± 13 ICM/NICM VT ablation All VT Non-randomized prospective single-centre trials i Niwano 2008 58 37 ± 7 ICM/NICM VT ablation All VT Mapping during VT/substrate mapping Mapping during VT/substrate mapping Mapping during VT/substrate mapping Mapping during VT/substrate mapping 51 (81%) 12 (3) 51% 9% c 113 (49%) 6 e 53% 18% f 59 (41%) 8 ± 5 46% 25% g 43 (74%) 31 ± 22 75% 16% Carbucicchioet al. 2008 8 95 36 ± 11 ICM/NICM/AR VC VT ablation Electrical storm Mapping during VT/substrate mapping 85 (89%) h 22 ± 13 63 (66%) 16% Wissner et al. Eur Heart J. 2012;33:1440-50

Ablation of LAVAs (Local Abnormal Ventricular Activities) Elimination of LAVAs: A new procedural endpoint for VT ablation Non-inducibility: 70% VT Recurrence or/and Death: 55% (All pts) 45% (LAVA elimination) 80% (no LAVA elimination) Jais et al. Circulation 2012;125:2184-2196

92 patients (81% male, mean age 62 ys) with ischemic cardiomyopathy and ES underwent catheter ablation 85% non-indusibility of any VT (82% in Endocardial Substrate Ablation and 88% in Homogenization of the Scar) Mean FU 25 ±10 months Di Biase et al. JACC 2012;60:132-41

Vergara et al. J Cardiovasc Electrophysiol 2012;23:621-627

Recommendations for Catheter Ablation Prevention of ventricular tachycardia recurrences in patients with left ventricular dysfunction and sustained ventricular tachycardia 2015 ESC Guidelines for management of pts with VAs & prevention of SCD. Europace 2015 Aug 29

VT episode: Accelerated by ATP, Terminated by Shock CL=350ms What would be the ideal timing for Catheter Abaltion? CL=270ms

Primary VT Ablation Trial Number of patients Inclusion criteria Comparator Follow-up (months) Primary endpoint SMASH- VT 1 unstable VT, or prior ICD and single 128 Prior MI, VF arrest, appropriate shock, criterion added later on: ICD for primary prevention and appropriate ICD therapy for a single event VTACH 2 secondary prevention with 107 Prior MI, stable VT, ICD, LVEF < 50 % ICD alone 24 Free from any appropriate ICD therapy ICD alone 22.5 Time to recurrence of VT/VF 1 Reddy et al NEJM 2007;357:2657-65 2 Kuck et al. Lancet 2010;375:31-40

Recommendations for Catheter Ablation Prevention of ventricular tachycardia recurrences in patients with left ventricular dysfunction and sustained ventricular tachycardia 2015 ESC Guidelines for management of pts with VAs & prevention of SCD. Europace 2015 Aug 29

The VANISH Trial 259 patients with previous MI,VT and ICD on AAD R Ablation (n=132) Escalated AAD* therapy (n=127) 1. Inclusion Criteria: 2. Prior MI 3. An ICD 4. One of the following VT events (within last 6 months): A. 3 episodes of VT treated with antitachycardia pacing (ATP), at least one of which is symptomatic. B. 1 appropriate ICD shocks, C. 3 VT episodes within 24 hr D. Sustained VT below detection rate of the ICD documented by ECG/cardiac monitor 5. Failed first-line antiarrhythmic drug therapy (Class 1 or 3) as defined by one of: A. Appropriate ICD therapy or sustained VT occurred while the patient was taking amiodarone (minimum cumulative dose of 10 g should have been administered to be considered a drug failure) B. Appropriate ICD therapy or sustained VT occurred on another antiarrhythmic drug or combination of antiarrhythmic drugs (patient on a stable dose for 2 weeks) * mean follow-up; 27.9±17.1 months Amiodarone if another agent had been used previously Higher dose of amiodarone (if <300 mg/d) Mexiletine added if the dose of amiodarone was already at least 300 mg/d Sapp et al. NEJM 2016;375:111-21

The VANISH Trial 259 patients with previous MI,VT and ICD on AAD Primary outcome: Composite of Death occurring at any time after randomization VT storm ( 3 documented episodes of VT within 24 hours) after a 30-day treatment period. Appropriate ICD shock after a 30-day treatment period. Death -14% R VT storm -34% Primary composite outcome -27% Ablation (n=132) 9% Escalated AAD* therapy (n=127) Appropriate ICD shock -23% P=0.86 P=0.19 P=0.08 P=0.04 * mean follow-up; 27.9±17.1 months Amiodarone if another agent had been used previously Higher dose of amiodarone (if <300 mg/d) Mexiletine added if the dose of amiodarone was already at least 300 mg/d Sapp et al. NEJM 2016;375:111-21

Procedural Complications: A major concern (Thermocool VT Ablation Trial) 231 patients, LVEF (median): 25%, Recurrent episodes of monomorphic VT (median, 11 in the preceding 6 months) Ablation abolished all inducible VTs in 49% of patients Free from recurrent VT: 53% Stevenson et al. Circulation 2008;118:2773-2782

VT in structural heart disease: reentry Ventricular Tachycardia Sinus rhythm

Multiple reentrant circuits in the same substrate

Προεπεμβατική εκτίμηση ασθενούς πριν από επέμβαση κατάλυσης για κοιλιακή ταχυκαρδία σε έδαφος δομικής καρδιακής νόσου ICD Interrogation Athens Bioclinic EP Department

A thorough voltage mapping Athens Bioclinic EP Department

A thorough voltage mapping Scale 0,5-1,5 mv Scale 0-0,5 mv Athens Bioclinic EP Department

Athens Bioclinic EP Department

Lesion setting Athens Bioclinic EP Department

Athens Bioclinic EP Department

65-years-old man with VHD and old anterior MI Prosthetic mechanical mitral and aortic valve CRT-D LVEF: 15-20% Sustain monomorphic VT multiple shock and ATP Varelas V1 V2 V3 V4 V5 V6 130 bpm

65-years-old man with VHD and old anterior MI Prosthetic mechanical mitral and aortic valve CRT-D LVEF: 15-20% Sustain monomorphic VT multiple shock and ATP Treatment with amiodarone incessant VT Ablation unattainable 105 bpm The patient demands ICD deactivation

ICD deactivation at the end stage of a disease Deactivation of the ICD prevents shocks which can be physically painful and psychologically stressful for the patient and his relatives, without prolonging a life of acceptable quality. 2015 ESC Guidelines for management of pts with VAs & prevention of SCD. Europace 2015 Aug 29 Ventricular tachyarrhythmia occurred in 35% of the patients in the last hour of their lives Kinch Westerdahl et al Circulation 2014;129:422-9

Συμπεράσματα Οι εκφορτίσεις του απινιδωτή επιβαρύνουν την ποιότητα ζωής και υπάρχουν σαφείς ενδείξεις για αρνητική επίδραση στην επιβίωση που αφορά το ευάλωτο μυοκαρδίου που παρουσιάζει κοιλιακές αρρυθμίες. Η φαρμακευτική αγωγή είναι η πρώτης επιλογής θεραπεία για τον περιορισμό των επεισοδίων κοιλιακής ταχυκαρδίας σε ασθενείς με δομική καρδιοπάθεια και απινιδωτή. Ο επαναπρογραμματισμός του απινιδωτή κατά τρόπον ώστε να αποφεύγονται οι εκφορτίσεις και να προτάσσεται η αντιταχυκαρδιακή βηματοδότηση είναι ένας χρήσιμος ελιγμός στην αντιμετώπιση των συχνών εκφορτήσεων, που έχει αποδειχθεί εξαιρετικά επωφελής στην πρωτογενή πρόληψη αλλά πιθανόν δεν αρκεί στη δευτερογενή. Η συνεισφορά της κατάλυσης στην αντιμετώπιση των πολλαπλών επεισοδίων κοιλιακής ταχυκαρδίας και της ηλεκτρικής θύελλας είναι κεφαλαιώδης, μειώνοντας τις εκφορτίσεις και βελτιώνοντας την ποιότητα ζωής. Σειρές παρατηρήσεις αλλά και τυχαιοποιημένες μελέτες έχουν δείξει ότι η κατάλυση είναι πιο αποτελεσματική και έχει μακροπρόθεσμα οφέλη στη μείωση του αρρυθμικού φορτίου όταν επιχειρείται νωρίς από την εμφάνιση κοιλιακής ταχυκαρδίας και εκφορτίσεων.

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