La gestione di un paziente con ICD: come evitare gli shock inappropriati e prolungare la sopravvivenza del paziente. Maurizio Gasparini

Transcription

1 La gestione di un paziente con ICD: come evitare gli shock inappropriati e prolungare la sopravvivenza del paziente Maurizio Gasparini Responsabile UO Elettrofisiologia ed Elettrostimolazione Humanitas Research Hospital, Rozzano-Milano

2

3 M. Gasparini La gestione di un paziente con ICD: come evitare gli shock inappropriati e prolungare la sopravvivenza del paziente Take home message ADVANCE III/ MADIT RIT a) In primary prevention VT< 180 bpm therapy always OFF b) high % of self terminating Fast VT/VF! longer Fast VT/VF detection window c) efficacy of ATP in fast VT d) VF cut off! should be programmed > 240 bpm

4 ICD programming! Even if life-saving, ICD shocks may be painful! " QOL! To improve QOL! " " /abolish inappropriate shocks! " " / abolish unnecessary shocks 2 strategies! on NSVT/VF! on VT suitable for ATP 1. ATP therapy 2. Correct detection window Consistent % of ventricular arrhythmias are self-terminating! (Painfree II 2004, Relevant 2009 ) ~70% of VT/fast VT interrupted by ATP without increased syncope or mortality (Painfree II 2004)

5 Cascade of Events Leading to ICD Shock Heart rate threshold Duration/ no. intervals Detection Enhancements Discrimination ATP If ineffective VT Tachycardia Shock Ignore slow rhythms (VT, SVT) Ignore nonsustained Ignore SVT Terminate VT Allow time self-term Terminate some SVT Morphology onset, stability, other logic Single/dual chamber

6 Evidence-based ATP is effective VA often self-terminating in few seconds 2012 ICD OUT-OF-THE BOX PROGRAMMING Still nominal settings for VF window of 1-3 seconds only, by major ICD manufacturers! 5,7 sec 3,3 sec 1 sec 2,4 sec Painfree II validated

7 5 programming variables VT on!?? 1500 pts PRIMARY PREVENTION randomized VT off! 3-arm study of patients randomized 1:1:1 VT on 60 sec! VT on 12 sec! Primary end-point: 1 st THERAPY OCCURENCE

8 Moss, NEJM 2012

9 Moss, NEJM % lost f.u

10

11 ADVANCE III Global, prospective, parallel, randomized, single-blinded, multi-center trial 94 active centers pts enrolled and randomized CAD and non-cad pts Primary and Secondary indication Median follow-up : 12 months All Medtronic ICD (Single/Dual/CRT) with ATP During Charging.

12 Primary End point To demonstrate a 20% " of ATP and Shocks! fast cycle length (CL 320 ms)! NID 30/40 compared to 18/24! Primary Prevention or Secondary Prevention! ANY ETIOLOGY! ANY Medtronic ICD (single/dual/crt)

13 Patients Flowchart Enrolled (n=1927) Excluded (n=24) Eligible (n=1903) Not Randomized (n=1) Randomized 1:1 (n=1902) 18/24 Arm (n=954) 30/40 Arm (n=948) Clinical data available for primary endpoint (n=891) Clinical data available for primary endpoint (n=876)

14 Device Programming # ATP during charging programmed ON in both groups Study group (VF NID 30/40 and ATP During Charging) Confirmation/ Synchronization Capacitor Charging 30/40 Shock Detection ATP 9.6 / 12.8 s 2.3 s 8.2 s 17.1 / 21 s Control group (VF NID 18/24 and ATP During Charging) 18/24 Detection Capacitor Charging ATP Confirmation/Synchronization Shock 5.8 / 7.7 s 2.3 s 8.2 s 14 / 15.9 s

15 Selected Baseline Data Comparable to previous studies (Pain Free II, EMPIRIC, PREPARE) Group 30/40 N=948 Group 18/24 N=954 Male gender, n (%) 795 (83.9%) 803 (84.2%) Age, (SD) 65 (11) 65 (11) Hypercholesterolemia, n (%) 499 (53.0%) 494 (52.0%) Diabetes, n (%) 275 (29.0%) 279 (29.3%) Chronic Kidney Disease, n (%) 130 (13.8%) 105 (11.1%) Angina, n (%) 126 (13.3%) 106 (11.3%) Syncopal episodes, n (%) 194(20.5%) 187 (19.6%) NYHA Class III or IV, n (%) 460 (49.2%) 447 (47.5%) Coronary Artery Disease, n (%) 567 (49.8%) 566 (59.3%) Previous Revascularization, n (%) 396 (41.8%) 395 (41.5%) Pts with CV hospitalizations, n (%) 466 (49.2%) 467 (49.0%) QRS (ms) 128 (35) 127 (35) LBB, n (%) 328 (34.6%) 303 (31,.8%) Mitral Regurcitation (III/IV), n (%) 107 (13.2%) 113 (13.9%) LVDD(mm) 64 (9) 64 (9) LVEF(%) 30 (10) 30 (10)

16 Selected Baseline Data Implanted System Group 30/40 Group 18/24 Secondary Prevention, n (%) 229 (24.2%) 248 (26.0%) CRTD 388 (40.9%) 387 (40.6%) Dual Chamber 293 (30.9%) 289 (30.3%) Single Chamber 267 (28.2%) 278 (29.1%) Atrial Arrhythmia History Group 30/40 Group 18/24 Permanent Atrial Fibrillation, n (%) 113 (12.3%) 99 (10.8%) Ventricular Arrhythmia History Group 30/40 Group 18/24 VF/V Flutter, n (%) 82 (8.7%) 92 (9.6%) Sustained VT 146 (15.4%) 160 (16.8%) OPT

17 Primary Endpoint Results # Median F.U. 12 months Therapies (ATP+Shock) Nr Pts Rate * 100 pts years Arm 30/ ( ) Arm 18/ ( ) IRR: 0.63 CI: , p<0.001

18 Primary Endpoint Results # Therapy free survival is significantly different /40 18/24 Kaplan Meier therapy-free survival estimate, by StudyArm Number at risk 30/40 18/24 p< months

19 Primary Endpoint Results # Time to first therapy is significantly different

20 Primary Endpoint Result Therapies Incidence Rate Ratio adjusted for center Therapies Incidence Rate Ratios adjusted for center 30/40 Better 18/24 Better 30\40 better 18\24 better ATP+shocks p<0.001 Shocks p=0.060 ATP p<

21 Primary Endpoint Result Therapies Incidence Rate Ratio adjusted for center

22 Secondary Efficacy Endpoint Results

23 Secondary Efficacy Endpoint Results # Time to first inappropriate shock is significantly different

24 Health Economic Outcomes Hospitalizations Hospitalizations (pts) rate * 100 patients/year IRR (95%CI) Control arm 473 (302) 51.7 ( ) 1 Long 392 (244) 42.1 ( ) 0.81 ( ) Detection p-value 0.027

25 Safety Syncopal events # no statistically significant difference in syncopal events associated with ventricular arrhythmic episodes. Rate : 1.6 syncope/100 pts year (comparable with previous studies) Arm Pts in the study ADVANCEIII Pts (%) events PainFREEII Pts (%) events PREPARE Pts (%) events 30/ (1,5%) 20 18/ (0.8%) 16 na (0.7%) 2 11 (1.6%) 12

26 Safety Syncopal events # no statistically significant difference in syncopal events associated with ventricular arrhythmic episodes. Control Arm Long Detection Therapies (ATP+Shock) Syncope Rate * 100 pts IRR (95% CI) s (pts) years 16 (14) 1.9 ( ) 1 24 (20) 3.1 ( ) 1.60 ( ) pvalue p=0.22

27 Safety Survival # Deaths: 106 (5,6%) patients : 49!30/40 arm and 57! 18/24 arm 1.00 Kaplan Meier survival estimate, by StudyArm 0.75 p= /40 18/ months Number at risk 30/ /

28 Primary Endpoint On Treatment Therapies (ATP+Shock) Intention to Treat Nr Pts Rate * 100 pts years Control arm ( ) Long ( ) Detection Therapies (ATP+Shock) On Treatment Nr Pts Rate * 100 pts years Control arm ( ) Long detection 38.0 ( ) IRR: 0.60 CI: , p<0.001

29 Conclusions # Advance III is the first randomized trial enrolling both PP and SP, CAD and non-cad, aiming to assess efficacy and safety of long NID detection in any ICD. # The long NID 30/40 detection window was effective in reducing unnecessary ICD therapies. # Long detection is associated with a reduction in the number of inappropriate shocks and allcause hospitalizations

30 PROVIDE study PRIMARY PREVENTION 1670 pts Aggressive 4,5 sec Conventional 3 sec 3 programming variables Saeed, JCE 2013

31 PAINFREE SST! PRIMARY and SECONDARY PREVENTION (2017 pts) 98.2% inappropriate shock free rate at 1 year DDD ICD/CRT-D 97.6% inappropriate shock free rate at 1 year VVI SMART SHOCK TECHNOLOGY

32 ADVANCE III MADIT RIT PROVIDE ENROLLED PTS (pts per arm) 1902 (954/948) 1500 (514/500/486) 1670 (846/824) WITHDRAWN/ LOST TO F.U. 3.2% 11.2% n.a. PRIMARY PREVENTION (pts) YES (1425) YES (1500) YES (1670) SECONDARY PREVENTION (pts) YES (477) NO NO PERMANENT AF YES NO YES ICD TYPE (VVI / DDD / CRTD) YES /YES / YES NO /YES / YES YES /YES / YES CONTROL ARM DETECTION SETTING PAINFREE II validated Out-of-the box/madit II Out-of-the box/prove CONTROL ARM NID 5,8 sec 1 sec 2.5 sec THERAPY ARM NID 9,6 sec 2,5 sec 4,5 sec VT THERAPY ACTIVATION VF CUT OFF OFF 300 bpm ON 200/240 bpm OFF 250 bpm PRIMARY END POINT ALL ICD THERAPIES FIRST INAPP. THERAPY FIRST SHOCK ALL ARRHYTHMIC ALL ARRHYTHMIC SYNCOPES ONLY FIRST SYNCOPE SYNCOPES SYNCOPES QUALITY OF LIFE YES NO NO HOSPITALIZATIONS YES NO YES

33 Benefits from long detection window confirmed in SP too! (Advance III substudy) Delivered ICD therapies SHOCK ATP p = NID 18/ 24 NID 30/ 40

34 Circ Arrhythm Electrophysiol Therapy reduction vs conventional programming and risk of death

35 Risk of syncope with therapy reduction vs conventional programming Tan, Circ Arrhythm Electrophysiol. 2014

36 Risk of inappropriate shocks with therapy reduction vs conventional programming Tan, Circ Arrhythm Electrophysiol. 2014

37

38 Heart Rhythm 2014

39

40 Take home message Evidence-based ICD programming derived from MADIT RIT, ADVANCE III, PROVIDE a) In primary prevention VT< 180 bpm therapy always OFF b) high % of self terminating Fast VT/VF! longer Fast VT/VF detection window c) efficacy of ATP in fast VT d) VF cut off! should be programmed > 240 bpm e) 3 positive trials primary prevention 1 positive trial secondary prevention too