1. Results from the PROVIDE Trial
Programming Implantable Cardioverter Defibrillators to Prolong Time to First Shock
Results from the PROVIDE Trial
Mohammad Saeed, MD
Robert Styperek, MD
Leo Polosajian, MD
Ahmed Khan, MD
Ibrahim Hanna, MD
Joseph Alonso, MD
Dionyssios Robotis, MD
Curtis Neason, BS
Linda Saberi, BS

2. Outline
Key Conclusions
Actual slides presented at HRS 2012

3. Key Conclusions
By utilizing a combination of specific programming parameters, shock therapy can be significantly reduced without increasing syncope, in patients with ICD implanted for primary prevention.
Majority of benefit was due to avoidance of inappropriate Shocks
Appropriate shock rate was low and not different between groups
There was no statistical difference between arrhythmic syncope among groups

4. Results from the PROVIDE Trial
Programming Implantable Cardioverter Defibrillators to Prolong Time to First Shock
Results from the PROVIDE Trial
Mohammad Saeed, MD
Robert Styperek, MD
Leo Polosajian, MD
Ahmed Khan, MD
Ibrahim Hanna, MD
Joseph Alonso, MD
Dionyssios Robotis, MD
Curtis Neason, BS
Linda Saberi, BS

5. Financial Disclosures
Mohammad Saeed, MD
Clinical Investigator: Medtronic, Boston Scientific, St. Jude.
Consultant/ Honoraria: Medtronic, Boston Scientific, St. Jude.
The PROVIDE Trial was sponsored in full by St. Jude Medical.

6. Background
SCD-HeFT1 and MADIT II2 have expanded the patient population eligible for ICDs to include primary prophylaxis of VT/VF.
Nearly half of all shocks experienced by this patient population are inappropriate.3
Inappropriate shocks and other avoidable shocks can lead to ICD battery depletion, a decrease in the patient’s quality of life4,5,6 and may be detrimental to cardiac function.
1 Bardy GH et al. N Engl J Med, Jan 2005.
2 Moss AJ et al. N Engl J Med, 2002.
3 Wilkoff B et al. JACC, Aug 2008.
4 Schron EB et al. Circ, 2002.
5 Irvine JD et al. Am Heart J, Aug 2002.
6 Carroll DL et al. J Acute Crit Care, May 2005.

7. Background
PainFREE Rx I1 & II2 showed that ATP is effective at terminating FVT in a broad ICD population.
The PROVE trial3 demonstrated that ATP is highly effective at terminating VT safely in primary prevention population.
EMPIRIC4 prescribed programming for all ICD recipients utilizing PF II programming and SVT discriminators.
The PREPARE5 trial suggested that prolong detection interval (NID 30/40) in addition to ATP might reduce shocks in the primary prevention population.
1 Wathen MS et al. Circ, Aug 2001.
2 Wathen MS et al. Circ, Oct 2004.
3 Saeed M et al. JCE, Dec 2010.
4 Wilkoff BL et al. JACC, Jul 2006.
5 Wilkoff BL et al. JACC, Aug 2008.

8. Background
However, PREPARE was non-randomized, used a historical control, and utilized programming changes limited only to the prolongation of detection intervals.1
Furthermore, programming an increased number of detection intervals in the VF detection zone may have contributed to the higher frequency of syncope in this study.1
Follow-up for PREPARE was 12 months. 1
1 Wilkoff BL, et al. JACC, Aug 2008.

9. Purpose
To study the efficacy and safety of a strategic combination of programming parameters in order to reduce shocks:
Higher detection rates
Prolonged detection intervals
Aggressive application of SVT discriminators
Use of ATP therapy for FVT
Patients receiving ICD for primary prevention of sudden cardiac death.

10. Methods Prospective, multi-center, randomized trial.
Patients receiving a de novo ICD or CRT-D manufactured by St. Jude Medical for primary prevention indication.
Visit schedule: Enrollment <30 days post implant and every 3 months until study conclusion.
Patients with an inducible sustained VT <181 bpm during an electrophysiology test were excluded.
All episodes were adjudicated by a panel of EPs to determine rhythm and success of therapy.

11. Methods Primary endpoint: Safety endpoint: Mean time to first shock
Rate of arrhythmic syncope

12. Device Programming Control [MONITOR] 2x ATP Shocks (12 beats)
Nominal SVTd
Experiment
2x ATP
Shocks
(25 beats)
1x ATP
(18 beats)
(12 beats)
Optimized SVTd
150 bpm
181 bpm
214 bpm
250 bpm

13. Device Programming Rationale for programming the Control Group
Utilized zones and therapies from PROVE Trial
One VT and VF zone along with monitor zone
Very successful at terminating VT with ATP
SVT discriminators were nominal settings except:
All SVTd were turned ON
SVTd Timeout was turned OFF
[MONITOR]
2x ATP
Shocks
(12 beats)
Nominal SVTd
Control
150 bpm
181 bpm
214 bpm

14. Device Programming Rationale for programming the Experiment Group
Zones and therapies based on PREPARE except:
Detection intervals were tiered to minimize syncope
Applied SVTd up to 214bpm (instead of 200 bpm)
Attempted a second round of ATP between bpm
SVT discriminators were based on literature
Theuns et al.1 for DR and CRT-D settings
Boriani et al.2 for SR settings
2x ATP
Shocks
(25 beats)
1x ATP
(18 beats)
(12 beats)
Optimized SVTd
Experiment
181 bpm
214 bpm
250 bpm
1 Theuns D et al. Heart Rhythm, Nov Boriani G et al. PACE, Sep 2002.

15. SVT Discriminators DR/CRT-D Control Experiment
SVT Discrimination Timeout
OFF
V<A, V=A
If Any
If All
MD % Match
60%
Stability Delta
80 ms
40 ms
Onset Delta
100 ms
16% SR
Control
Experiment
SVT Discrimination Timeout
OFF
VT Diagnosis
If Any
If 2 of 3
MD % Match
60%
Interval Stability ON
ON w/ SIH
Stability Delta
80 ms
40 ms
Onset Delta
100 ms
16%

16. Results All Patients (N=1670) Control (N=824) Experiment (N=846)
P-value
Follow-up Duration (days) , Mean, Range
548,
531,
565,
0.002
Age (years), Mean ± SD
64 ± 13
64 ± 12 ns
Gender, N
1219 (73%)
599 (73%)
620 (73%)
NYHA Class I
79 (5%)
33 (4%)
46 (5%) II
520 (31%)
264 (32%)
256 (30%)
III
782 (47%)
381 (46%)
401 (48%) IV
26 (2%)
8 (1%)
18 (2%)
UNK
263 (16%)
138 (17%)
125 (15%)
LVEF (%), Mean ± SD
27 ± 9
27 ± 10
QRS Dur (ms), Mean ± SD
124 ± 32
123 ± 31
124 ± 33
Cardiomyopathy
Ischemic
1040 (62%)
510 (62%)
530 (63%)
Non-Ischemic
630 (38%)
314 (38%)
316 (37%)

17. Results All Patients (N=1670) Control (N=824) Experiment (N=846)
P-value
Cardiac History
Prior MI
817 (49%)
412 (50%)
412 (48%) ns
Unstable Angina
180 (11%)
76 (9%)
104 (12%)
0.05
CABG
519 (31%)
258 (31%)
261 (31%)
PTCA/Stents/Atherectomy
639 (38%)
313 (38%)
326 (39%)
Other Medical Conditions
Diabetes
600 (36%)
300 (36%)
COPD
220 (13%)
115 (14%)
105 (12%)
Hyperlipidemia
1005 (60%)
497 (60%)
508 (60%)
Hypertension
1213 (73%)
607 (74%)
606 (72%)
Peripheral Vascular Disease
150 (9%)
80 (10%)
70 (8%)
Renal Disease
191 (11%)
105 (13%)
86 (10%)
Valvular Disease
227 (14%)
112 (13%)

18. Results All Patients (N=1670) Control (N=824) Experiment (N=846)
P-value
Cardiac Medications, n (%)
ACE Inhibitor
1015 (61%)
504 (61%)
511 (60%) ns
Antiarrhythmic, Class I
19 (1%)
10 (1%)
9 (1%)
Antiarrhythmic, Class III
155 (9%)
73 (9%)
82 (10%)
ARB
305 (18%)
148 (18%)
157 (19%)
Beta Blocker
1482 (89%)
734 (89%)
748 (88%)
Calcium Channel Blocker
154 (9%)
76 (9%)
78 (9%)
Diuretic
1092 (65%)
566 (69%)
526 (62%)
0.01
Nitrate
315 (19%)
159 (19%)
156 (18%)
Aldosterone Inhibitor
295 (18%)
147 (17%)
Anti-coagulant
491 (29%)
227 (28%)
264 (31%)
Anti-platelet
1125 (67%)
564 (68%)
561 (66%)
Arrhythmia History
Atrial Fibrillation
443 (27%)
210 (25%)
233 (28%)
Atrial Flutter
56 (3%)
27 (3%)
29 (3%)
Sinus Tachycardia
54 (3%)
25 (3%)
Atrial Tachycardia
13 (0.8%)
5 (0.6%)
8 (0.9%)

19. Device Type
22%
41%
37%
p = ns
22%
40%
38%

20. Results: Primary Endpoint
Time to First Shock : All-Cause 25
Control
Experiment
18.7
% Patients 20
p = 15
12.3 10
10.3 5
7.0
0.5
1.0
1.5
2.0
Years
N at Risk
Control
824
671
542
313
141
Experiment
846
729
599
392
190

21. Results: Primary Endpoint
Time to First Shock - Appropriate
Control
Experiment 25
% Patients 20 15
p = 0.69 10
4.9
3.0 5
4.9
2.8
0.5
1.0
1.5
2.0
Years
N at Risk
Control
824
716
592
347
160
Experiment
846
749
625
406
196

22. Results: Primary Endpoint
Time to First Shock - Inappropriate
Control
Experiment 25
% Patients 20
13.8 15
p <
9.3 10 5
5.4
4.1
0.5
1.0
1.5
2.0
Years
N at Risk
Control
824
683
559
331
153
Experiment
846
743
616
411
199

23. Results: Safety Endpoint
Time to First Arrhythmic Syncope 10
Control
Experiment
% Patients
Number of Arrhythmic Syncopal Episodes
Control 8
Experimental 14 5
p = 0.27
0.5
1.0
1.5
2.0
Years
N at Risk
Control
824
726
607
360
169
Experiment
846
759
635
415
201

24. Conclusions
By utilizing a combination of specific programming parameters, shock therapy can be significantly reduced without increasing syncope, in patients with ICD implanted for primary prevention.
Majority of benefit was due to avoidance of inappropriate Shocks
Appropriate shock rate was low and not different between groups
There was no statistical difference between arrhythmic syncope among groups

25. Recommendations
The following programming parameters should be considered when implanting ICDs in primary prevention patients:
Monitor zone OFF
Lower rate cutoff for VT zone at 180 bpm
Lower rate cutoff for VF zone at 250 bpm
Prolonging the detection intervals
SVTd ON with sustained rate timer OFF
Empiric ATP for FVT up to 250bpm