1. 1 Version 1, 2/21/02, DRAFT Medtronic InSync ® ICD Cardiac Resynchronization System FDA Advisory Panel March 5, 2002

2. 2 Version 1, 2/21/02, DRAFT Agenda Background and IntroductionDr. William Abraham 10 minutes Study Design and MethodologyDr. James Young 10 minutes Safety and Lead Effectiveness Results Dr. Angel Leon 20 minutes Efficacy ResultsDr. James Young 15 minutes Comparison to InSync and Conclusions Dr. William Abraham 10 minutes

3. 3 Version 1, 2/21/02, DRAFT Introduction and Background William T. Abraham, MD

4. 4 Version 1, 2/21/02, DRAFT Introduction Over a third of moderate to severe heart failure patients (in NYHA Functional Class III or IV) have ventricular dysynchrony, evidenced by a QRS duration  130 ms 1 Associated with Limited exercise tolerance Impaired quality of life and functional capacity Poor left ventricular systolic function 2 1 Aaronson KD, et al. Circulation 1997; 95:2660-2667. 2 Zardini M, et al. Eur Heart J 2000; 2(Suppl J): J16-J22

5. 5 Version 1, 2/21/02, DRAFT InSync Study Design Baseline Implant Attempt Successful Implant Control CRT Pre-discharge Randomization 1, 3, 6 Month Follow-up 1, 3, 6 Month Follow-up CRT Double Blinded Stable Medical Therapy  1 week CRT Long term follow up every 6 months Control: VDI mode Treatment (CRT): VDD mode

6. 6 Version 1, 2/21/02, DRAFT InSync Study Primary Endpoints* EndpointControlCRTp value Quality of Life (points) 918.50.003 NYHA Class01<0.001 6-minute walk (meters) 10400.003 * PMA# P010015, approved 8/28/01

7. 7 Version 1, 2/21/02, DRAFT InSync Study Secondary Clinical Endpoints <0.001  66,  20,  14  42,  35,  23 Composite Response (%) <0.0018512Exercise Time (sec) 0.0381.00.1Peak VO2 (ml/kg/min) P valueCRTControlEndpoint

8. 8 Version 1, 2/21/02, DRAFT InSync Primary Safety Results Summary Achieved all primary 6-month safety objectives including: Implant success 6-month device related complications attributed to: InSync Model 8040 Attain Models 2187 and Model 2188 LV leads InSync system Attain Models 2187 and 2188 LV lead 6-month pacing threshold

9. 9 Version 1, 2/21/02, DRAFT InSync Death or Worsening Heart Failure Requiring Hospitalization or IV Medications 73157162184211219230— CRT 62150157178197209231— Control Patients At Risk P = 0.02 CRT Control

10. 10 Version 1, 2/21/02, DRAFT Model 7272 InSync ICD Dual-chamber VT and VF detection Antitachycardia (ATP) pacing, cardioversion and defibrillation VT and VF therapies Simultaneous biventricular pacing RV sensing only Combining Resynchronization and ICD Function in a Single Device

11. 11 Version 1, 2/21/02, DRAFT Study Design, Methodology and Patient Population James B. Young, MD

12. 12 Version 1, 2/21/02, DRAFT Entry Criteria Chronic heart failure  18 years of age NYHA Functional Class II, III or IV QRS duration  130 ms LVEF  35% LVEDD  55 millimeters (echo measure) Stable HF medical regimen for  1 month ACE-I or substitute, if tolerated β-blocker - stable regimen for  3 months Indication for an ICD

13. 13 Version 1, 2/21/02, DRAFT InSync ICD Study Design Baseline Implant Attempt Successful Implant Control CRT Pre-discharge Randomization 1, 3, 6 Month Follow-up 1, 3, 6 Month Follow-up CRT Double Blinded Stable Medical Therapy  1 week CRT Long term follow up every 6 months Control: DDI mode Treatment (CRT): DDD mode ICD active in all patients Heart failure medication stability maintained

14. 14 Version 1, 2/21/02, DRAFT Timing of Baseline Tests TestInSyncInSync ICD 6-Minute Hall Walk0-7 days pre-implant Cardiopulmonary Exercise Test 0-7 days pre-implant 0-7 days post-implant QOL Questionnaire 0-7 days pre-implant NYHA0-7 days pre-implant

15. 15 Version 1, 2/21/02, DRAFT Study Features to Maintain the Blind Blinded: Patients (study ID card) Heart failure staff Listed on study blinding log Blinded to ECGs Conducted QOL, 6 minute hall walk, patients global assessment, NYHA classification and HF exam Events Classification Committee Unblinded: EP staff Listed on study blinding log Viewed ECGs, device printouts, etc Data placed into secure study envelopes

16. 16 Version 1, 2/21/02, DRAFT Primary Safety Objectives InSync ICD-related complication-free survival at 3 months Attain Model 4189 LV lead-related complication-free survival at 6 months Attain Model 2187/2188 LV lead- related complication-free survival at 6 months InSync ICD system-related complication-free survival at 6 months

17. 17 Version 1, 2/21/02, DRAFT Secondary Safety Objectives Characterize patient survival Characterize complication events Characterize observation events

18. 18 Version 1, 2/21/02, DRAFT Lead Effectiveness Objectives Implant success Evaluate the electrical performance of the Model 4189 LV lead Evaluate the electrical performance of the Model 2187 and Model 2188 LV leads

19. 19 Version 1, 2/21/02, DRAFT Evaluation of Integrity of ICD Function Spontaneous VT/VF therapy effectiveness Comparison of VT/VF event rates in the control and treatment arms ATP therapy efficacy with biventricular pacing Implant ventricular defibrillation criterion

20. 20 Version 1, 2/21/02, DRAFT Primary Effectiveness Endpoints As pre-specified in the investigational plan for NYHA Class III and IV patients, the following change from baseline to 6-month visit between control and treatment groups in: Quality of life (MLWHF Questionnaire) NYHA class 6-minute hall walk distance As pre-specified in the investigational plan, all 3 endpoints must be met at P < 0.05, or 2 met at P < 0.025, or 1 met at P < 0.0167

21. 21 Version 1, 2/21/02, DRAFT Secondary Effectiveness Endpoints Clinical endpoints Exercise performance Clinical composite response Health care utilization Physiological variables Echocardiographic variables QRS duration Neurohormonal variables

22. 22 Version 1, 2/21/02, DRAFT Study Milestones 1999200020012002 1 st implant October 4, 1999 PMA submitted May 3, 2001 100 NYHA Class III & IV 6-month visits March, 2001 224 NYHA Class III & IV 6-month visits October, 2001 PMA Update submitted November 9, 2001

23. 23 Version 1, 2/21/02, DRAFT Patient Disposition Implant Attempts n=636 Randomized n=362 NYHA Class III/IV n=421 Control n=176 CRT n=186 NYHA Class II n=215 Randomized n=192 Control n=106 CRT n=86 As pre-specified in the I.P., data from NYHA Class III/IV patients are discussed in this presentation

24. 24 Version 1, 2/21/02, DRAFT Patient Disposition Implant Attempts n=421 Unsuccessful Implants n=50 Randomized n=362 Not Randomized n=9 Implant Success n=371 Control n=176 CRT n=186

25. 25 Version 1, 2/21/02, DRAFT Patient Disposition Control n = 176 CRT n = 186 1246 Month Dataset133 35Still in DB F/U36 15Death12 26 month F/U Visit Missed5

26. 26 Version 1, 2/21/02, DRAFT Methodology Overview Safety Data As pre-specified in the investigational plan, data from NYHA Class II, III and IV patients were submitted to FDA for the primary safety objectives At FDA’s request, safety data from NYHA Class III and IV patients only are included in the Panel Pack and in this presentation

27. 27 Version 1, 2/21/02, DRAFT Methodology Overview Efficacy Data The investigational plan pre-specified that the primary efficacy analysis was to be based on patients with paired data at 6 months, excluding crossovers Results presented are based on an intent-to-treat analysis for patients with paired data at 6 months, including crossovers Results of the pre-specified crossover excluded and last-observation-carried forward analyses will also be summarized

28. 28 Version 1, 2/21/02, DRAFT Control n=176 CRT n=186 Age, years (mean ± sd)68 ± 9 67  11 Gender (% male)77%76% NYHA (% Class III)89%88% QRS duration, ms (mean ± sd)162 ± 22165 ± 22 LVEF, % (mean ± sd)20 ± 621 ± 7 LVEDD, mm (mean ± sd)71 ± 970 ± 9 Heart Failure Etiology (% ischemic)74%63% Patient Demographics

29. 29 Version 1, 2/21/02, DRAFT Control n=176 CRT n=186 Peak VO 2, ml/kg/min (mean ± sd)13.5 ± 4.113.5 ± 3.7 6-Min Walk Distance, meters (mean ± sd)247 ± 118245 ± 127 Heart Rate, bpm (mean ± sd)72 ± 1371 ± 12 SBP, mmHg (mean ± sd)111 ± 17112 ± 20 DBP, mmHg (mean ± sd)67 ± 1366 ± 11 Diuretic Use94%93% ACE-I or ARB Use88%91% Beta-blocker Use57%63% Patient Demographics

30. 30 Version 1, 2/21/02, DRAFT Safety Results Angel R. Leon, MD

31. 31 Version 1, 2/21/02, DRAFT Primary Safety Objectives InSync ICD-related complication-free survival at 3 months Attain Model 4189 LV lead-related complication-free survival at 6 months Attain Model 2187/2188 LV lead- related complication-free survival at 6 months InSync ICD system-related complication-free survival at 6 months

32. 32 Version 1, 2/21/02, DRAFT Secondary Safety Objectives Characterize patient survival Characterize complication events Characterize observation events

33. 33 Version 1, 2/21/02, DRAFT Lead Effectiveness Objectives Implant success Evaluate the electrical performance of the Model 4189 LV lead Evaluate the electrical performance of the Model 2187 and Model 2188 LV leads

34. 34 Version 1, 2/21/02, DRAFT Evaluation of Integrity of ICD Function Spontaneous VT/VF therapy effectiveness Comparison of VT/VF event rates in the control and treatment arms ATP therapy efficacy with biventricular pacing Implant ventricular defibrillation criterion

35. 35 Version 1, 2/21/02, DRAFT Lead Placement and LV Venous Anatomy A. Lateral (marginal) cardiac vein B. Postero-lateral cardiac vein C. Posterior cardiac vein D. Middle cardiac vein E. Great cardiac vein E D A B C Attain LV Model 4189 Transvenous, 4 French Stylet/catheter Delivered Unipolar

36. 36 Version 1, 2/21/02, DRAFT Adverse Event Definitions Complication: An adverse event requiring invasive intervention or that results in the death of or serious injury to the patient or in the termination of a significant device function Observation: An adverse event not requiring invasive intervention or resolves spontaneously System-related complication: A device-related complication that occurs after the initially implanted functioning system, comprised of: Model 7272 InSync ICD, a Model 4189, 2187 or 2188 LV lead, and RA and RV leads

37. 37 Version 1, 2/21/02, DRAFT Implant Success Patient Implant Attempts n=421 Unsuccessful Implants n=50 Implant Success n=371 Implant success defined per the protocol as a successfully placed LV lead.

38. 38 Version 1, 2/21/02, DRAFT Unsuccessful Implants (n=50) Reason * n Dislodgement/unstable position24 Unable to obtain distal location18 Unable to cannulate coronary sinus ostium16 Unacceptable pacing thresholds 13 Dissection/perforation13 Unable to access coronary vein8 Coronary vein too small3 Patient decompensation during implant3 Delivery system/tool problems3 Patient venous anatomy2 Diaphragmatic stimulation2 Complete heart block1 * Not mutually exclusive

39. 39 Version 1, 2/21/02, DRAFT Adverse Events During the Implant Procedure 371 Successful Implants (53 Events) 50 Unsuccessful Implants (26 Events) Coronary Sinus Dissection512 Heart Block93 Pericardial Effusion23 Ventricular Tachycardia23 Atrial Fibrillation40 Cardiac Perforation32 Heart Failure Decompensation30 Hypotension21 Atrial Flutter20 Events Occurring One Time212

40. 40 Version 1, 2/21/02, DRAFT Resolution of Adverse Events During the Implant Procedure Resolution* 371 Successful Implants (53 Events) 50 Unsuccessful Implants (26 Events) No Intervention Required119 Pharmacological Therapy143 Reprogram Generator60 Lead Repositioned40 Lead Explanted01 Other Treatment3116 *Categories not mutually exclusive.

41. 41 Version 1, 2/21/02, DRAFT Resolution of Implant Dissection/Perforation Events 432 implant attempts 22 events (22 patients) EventsPatients No Intervention88 Procedure Abandoned77 Pericardiocentesis22 Hospitalized for observation22 Echocardiogram11 LV lead explanted / port plugged11 Lead repositioned11 No patient deaths related to these events.

42. 42 Version 1, 2/21/02, DRAFT Primary Safety Objective 1: Freedom From InSync ICD Related Complications at 3 Months Performance Objective 371 patients implanted 7 complications in 7 patients Observed 3-month rate = 98.6% Lower 95% confidence bound = 97.6% Performance objective: 95% LCB  89%

43. 43 Version 1, 2/21/02, DRAFT Freedom From InSync ICD Related Complications at 3 Months 371 patients implanted 7 events (7 patients) EventsPatients Pocket seroma/hematoma22 Pain at pocket site11 Abnormal impedance measurement11 Dizziness11 Electrical reset of ICD11 Pocket infection11

44. 44 Version 1, 2/21/02, DRAFT Primary Safety Objective 2: Freedom From Attain Model 4189 LV Lead-Related Complications at 6 Months Performance Objective 315 patients implanted 49 events (in 44 patients) Observed 6-month rate = 85.1% Lower 95% confidence bound = 81.7% Performance objective: 95% LCB  75%

45. 45 Version 1, 2/21/02, DRAFT Freedom From Attain Model 4189 LV Lead-Related Complications at 6 Months 315 patients implanted 49 events (44 patients) EventsPatients* Lead dislodgment2926 Extra cardiac stimulation11 Elevated pacing thresholds44 Failure to capture33 Muscle stimulation – pectoral11 Pericardial effusion11 * Not mutually exclusive

46. 46 Version 1, 2/21/02, DRAFT Attain Model 4189 LV Lead Related Complication Event Resolution Resolution*Events*Patients* Lead repositioned3230 Lead replaced10 Lead explanted77 ICD reprogrammed44 None, continue to follow44 Pericardiocentesis11 Extend/change lead route11 Lead setscrew retightened11 ICD replacement11 * Not mutually exclusive

47. 47 Version 1, 2/21/02, DRAFT Primary Safety Objective 3: Freedom From Attain Model 2187/2188 LV Lead-Related Complications at 6 Months Performance Objective 56 patients implanted 5 events in 5 patients Observed 6-month rate = 89.9% Lower 95% confidence bound = 82.9% Performance objective: 95% LCB  75%

48. 48 Version 1, 2/21/02, DRAFT Freedom From Attain Model 2187/2188 LV Lead-Related Complications at 6 Months 56 patients implanted 5 events (5 patients) EventsPatients Lead dislodgment33 Failure to capture11 Elevated pacing thresholds11

49. 49 Version 1, 2/21/02, DRAFT Primary Safety Objective 4: InSync ICD System-Related Complications at 6 Months Events related to: Left ventricular lead Right atrial lead 54 11 InSync ICD8 Right ventricular lead4 System2 Performance Objective 371 patients implanted 79 events in 65 patients Observed 6 month rate = 81.1% Lower 95% confidence bound = 77.6% Performance objective: 95% LCB  67%

50. 50 Version 1, 2/21/02, DRAFT Primary Safety Results: Summary All primary safety objectives satisfied Device-related complications attributed to: InSync ICD Model 7272 Attain Models 4189, 2187 and 2188 leads InSync ICD system

51. 51 Version 1, 2/21/02, DRAFT Secondary Safety Results

52. 52 Version 1, 2/21/02, DRAFT Spontaneous VT/VF Therapy Effectiveness Detection Zone # Patients # Episodes # Successfully Terminated # Unsuccessfully Terminated* % Successfully Terminated FVT14135133298.5% VF41128127199.2% VT50862855799.2% Overall78112511151099.1% * VT terminated after all therapies were delivered (5 episodes) FVT/VT terminated after redetection but before additional therapies could be delivered (4 episodes) VF terminated after all therapies were delivered (1 episode)

53. 53 Version 1, 2/21/02, DRAFT VT/VF Episodes Control vs. CRT Patients Completing 6 Months of Follow-up Control (n=116) CRT (n=125) Number of Patients with VT/VF (P=0.21) 29 (25.0%)22 (17.6%) Total Number of Episodes (P=0.15) 285156 Episodes per Month0.420.21

54. 54 Version 1, 2/21/02, DRAFT ATP Efficacy During Spontaneous VT ATP Site RV onlyRV + LV Number of Episodes294523 Successfully Terminated with ATP (P<0.0001) 247 (84%)493 (94%)

55. 55 Version 1, 2/21/02, DRAFT Ventricular Defibrillation Testing Implant Criterion Used nPercent (% ) 2 at  24 joules 29579.5% Binary Search 5214.0% Other246.5%

56. 56 Version 1, 2/21/02, DRAFT Lead Effectiveness Results

57. 57 Version 1, 2/21/02, DRAFT Lead Effectiveness Objective 1: Implant Success Results Performance Objective: Lower 95% Confidence Limit > 83% Results: Observed rate: 371 successes / 421 attempts = 88.1% Lower Limit of 2-Sided 95% C.I. = 84.6% Implant success defined per the protocol as a successfully placed LV lead.

58. 58 Version 1, 2/21/02, DRAFT Lead Effectiveness Objective 2: Attain Model 4189 LV Lead Pacing Threshold Performance Performance Objective: The upper 95% confidence bound for the mean pacing voltage threshold is < 3.0 Volts Results: Mean 6-month pacing threshold = 1.5 Volts  0.9 Volts Upper limit of 2-sided 95% confidence interval = 1.7 Volts

59. 59 Version 1, 2/21/02, DRAFT Voltage Pacing Threshold for Attain Model 4189 LV Leads 1.7 1.5 1.61.5 n=441 n=424 n=416n=381n=306n=125n=35

60. 60 Version 1, 2/21/02, DRAFT Lead Effectiveness Objective 3: Attain Model 2187/2188 LV Lead Pacing Threshold Performance Performance Objective: The upper 95% confidence bound for the mean pacing voltage threshold is < 3.0 Volts Results: Mean 6-month pacing threshold = 1.9 Volts  1.0 Volts Upper limit of 2-sided 95% confidence interval = 2.2 Volts

61. 61 Version 1, 2/21/02, DRAFT Voltage Pacing Threshold for Attain Model 2187/2188 LV Leads 1.7 1.9 2.31.9 1.7 1.6 n=79 n=82 n=79n=74n=62n=29n=18

62. 62 Version 1, 2/21/02, DRAFT Effectiveness Results James B. Young, MD

63. 63 Version 1, 2/21/02, DRAFT Primary Efficacy Endpoints QOL score NYHA class 6 minute hall walk distance Change from baseline to 6-month follow up between control and treatment groups in:

64. 64 Version 1, 2/21/02, DRAFT Change in Quality of Life Score Control n = 119 CRT n = 128 Baseline 6 Months  = -10  = -19 P=0.0098 Score (Median)

65. 65 Version 1, 2/21/02, DRAFT Change in NYHA Functional Class P=0.028

66. 66 Version 1, 2/21/02, DRAFT Change in NYHA Functional Class Control (n = 123)CRT (n = 131)

67. 67 Version 1, 2/21/02, DRAFT Change in 6-Minute Hall Walk Distance Control n = 118 CRT n = 122 Baseline 6 Months  = 53  = 56 P=0.408 Distance Walked (Median)

68. 68 Version 1, 2/21/02, DRAFT Summary of Effect on Primary Endpoints P-Values Endpoint Intention- to-Treat Per Protocol Intention- to-Treat Last Observation Carried Forward QOL0.00980.00440.003 NYHA0.0280.01450.02 6 Minute Hall Walk0.4080.49930.25

69. 69 Version 1, 2/21/02, DRAFT Secondary Effectiveness Results

70. 70 Version 1, 2/21/02, DRAFT Secondary Effectiveness Endpoints Clinical endpoints Exercise performance Clinical composite response Healthcare utilization Physiological variables Echocardiographic variables QRS duration Plasma neurohormones

71. 71 Version 1, 2/21/02, DRAFT Secondary Effectiveness Results: Clinical Endpoints

72. 72 Version 1, 2/21/02, DRAFT Exercise Performance Peak VO 2 and Exercise Duration Baseline 6 Months Control n = 93 CRT n = 96  = 0.0  = 1.1 P=0.05 Control n = 96 CRT n = 97  = -26  = 58 P=<0.001

73. 73 Version 1, 2/21/02, DRAFT Clinical Composite Response - Definition Improved Improved NYHA class or global assessment Worsened Death; worsening heart failure leading to hospitalization or permanent withdrawal of therapy; or worsening of NYHA class or global assessment No Change Packer et al. J Cardiac Failure 2001;7:176-182.

74. 74 Version 1, 2/21/02, DRAFT Clinical Composite Response Results P = 0.038

75. 75 Version 1, 2/21/02, DRAFT Hospitalization Results Total Days Hospitalized Through 6 Months All-Cause Hospitalization * Heart Failure Hospitalization # Control (n=176) CRT (n=186) * Control Group: 134 hospitalizations (79 pts) CRT Group: 127 hospitalizations (75 pts) # Control Group: 70 hospitalizations (47 pts) CRT Group: 54 hospitalizations (39 pts) P = 0.18 P = 0.11

76. 76 Version 1, 2/21/02, DRAFT InSync ICD Death or Worsening Heart Failure Requiring Hospitalization or IV Medications 55102117137153170186— CRT 469396117137148176— Control Patients At Risk P = 0.07 CRT Control

77. 77 Version 1, 2/21/02, DRAFT Secondary Effectiveness Results: Physiological Variables

78. 78 Version 1, 2/21/02, DRAFT Change in Echo Parameters ControlCRTP-value LV End Diastolic Volume-5-250.046 LV End Systolic Volume-8-260.04 LV Ejection Fraction1.63.00.06 Cardiac Index-0.020.030.89 Mitral regurgitation-0.5-0.40.98 LV Inflow E Wave Max Velocity0.5-10.00.03 LV Inflow A Wave Max Velocity6.5-4.00.04

79. 79 Version 1, 2/21/02, DRAFT Change in Echo/ECG Parameters ControlCRTP-value LV E-Wave/A-Wave Ratio-0.03-0.060.82 Normalized LV Filling Time0.010.050.001 LV Mass-6-30.97 LV Diameter in Systole-0.3-0.20.98 LV Diameter in Diastole-0.1-0.30.85 Interventricular Mechanical Delay-2-180.12 QRS Width-6-200.01

80. 80 Version 1, 2/21/02, DRAFT Change in Neurohormone Levels ControlCRTP-value Brain Natriuretic Peptide (BNP) -3-380.41 Dopamine0.0 0.56 Norepinephrine-38.010.50.24 Epinephrine-4.00.00.03 Big Endothelin-0.5 0.88

81. 81 Version 1, 2/21/02, DRAFT Comparison of InSync and InSync ICD William T. Abraham, MD

82. 82 Version 1, 2/21/02, DRAFT InSync ICD Study Design Baseline Implant Attempt Successful Implant Control CRT Pre-discharge Randomization 1, 3, 6 Month Follow-up 1, 3, 6 Month Follow-up CRT Double Blinded Stable Medical Therapy  1 week CRT Long term follow up every 6 months Control: DDI mode Treatment (CRT): DDD mode ICD active in all patients Heart failure medication stability maintained

83. 83 Version 1, 2/21/02, DRAFT Timing of Baseline Tests TestInSyncInSync ICD 6-Minute Hall Walk0-7 days pre-implant Cardiopulmonary Exercise Test 0-7 days pre-implant 0-7 days post-implant QOL Questionnaire 0-7 days pre-implant NYHA0-7 days pre-implant

84. 84 Version 1, 2/21/02, DRAFT InSync ICD n=362 InSync n=532 Age, years (mean ± sd)67 ± 10 64  11 Gender (% male)77%70% NYHA (% Class III)88%90% QRS duration, ms (mean ± sd)164 ± 22166 ± 21 LVEF, % (mean ± sd)20 ± 722 ± 6 LVEDD, mm (mean ± sd)71 ± 969 ± 10 Heart Failure Etiology (% ischemic)69%55% Comparison of Patient Demographics – InSync and InSync ICD

85. 85 Version 1, 2/21/02, DRAFT InSync ICD n=362 InSync n=532 Peak VO 2, ml/kg/min (mean ± sd)13.5 ± 3.913.8 ± 3.7 6-MW Distance, meters (mean ± sd)246 ± 123298 ± 97 Heart Rate, bpm (mean ± sd)71 ± 1374 ± 13 SBP, mmHg (mean ± sd)111 ± 18112 ± 19 DBP, mmHg (mean ± sd)66 ± 1268 ± 11 Diuretic Use93% ACE-I or ARB Use90%91% Beta-blocker Use60%56% Comparison of Patient Demographics – InSync and InSync ICD

86. 86 Version 1, 2/21/02, DRAFT Change in Quality of Life Score (InSync ICD vs. InSync) P=0.010 P=0.003 InSyncInSync ICD

87. 87 Version 1, 2/21/02, DRAFT P=0.02 P<0.001 InSync InSync ICD Change in NYHA Class (InSync ICD vs. InSync)

88. 88 Version 1, 2/21/02, DRAFT Change in 6-Minute Hall Walk Distance (InSync ICD vs. InSync) P=0.408 P=0.003 InSync InSync ICD

89. 89 Version 1, 2/21/02, DRAFT InSync and InSync ICD Studies: Primary Endpoints 0.003 0.408 +40 +56 +10 +53 6-minute walk (meters) <0.001 0.027 0000 NYHA Class (class) 0.003 0.010 -18.5 -19 -9 -10 Quality of Life (points) P-valueCRTControlEndpoint White = InSync Study; Yellow = InSync ICD Study

90. 90 Version 1, 2/21/02, DRAFT InSync and InSync ICD Studies: Secondary Clinical Endpoints <0.001 0.038  66,  20,  14  55,  19,  26  42,  35,  23  40,  26,  33 Composite Response (%) <0.001 85 58 12 -26 Exercise Time (sec) 0.038 0.050 1.0 1.1 0.1 0.0 Peak VO2 (ml/kg/min) P-valueCRTControlEndpoint White = InSync Study; Yellow = InSync ICD Study

91. 91 Version 1, 2/21/02, DRAFT InSync ICD Death or Worsening Heart Failure Requiring Hospitalization or IV Medications 55102117137153170186— CRT 469396117137148176— Control Patients At Risk P = 0.07 CRT Control

92. 92 Version 1, 2/21/02, DRAFT InSync Death or Worsening Heart Failure Requiring Hospitalization or IV Medications 73157162184211219230— CRT 62150157178197209231— Control Patients At Risk P = 0.02 CRT Control

93. 93 Version 1, 2/21/02, DRAFT Hospitalization Results: InSync ICD Total Days Hospitalized Through 6 Months All-Cause Hospitalization * Heart Failure Hospitalization # Control (n=176) CRT (n=186) * Control Group: 134 hospitalizations (79 pts) CRT Group: 127 hospitalizations (75 pts) # Control Group: 70 hospitalizations (47 pts) CRT Group: 54 hospitalizations (39 pts) P = 0.18 P = 0.11

94. 94 Version 1, 2/21/02, DRAFT Hospitalization Results: InSync Total Days Hospitalized Through 6 Months All-Cause Hospitalization * Heart Failure Hospitalization # Control (n=231) CRT (n=230) *Control Group: 99 hospitalizations (60 pts) CRT Group: 80 hospitalizations (57 pts) #Control Group: 39 hospitalizations (27 pts) CRT Group: 20 hospitalizations (14 pts) P=0.002 P=0.083

95. 95 Version 1, 2/21/02, DRAFT The End