1. Author Disclosures Differences in Implantation-Related Adverse Events Between Men and Women Receiving ICD Therapy for Primary Prevention Differences in Implantation-Related Adverse Events Between Men and Women Receiving ICD Therapy for Primary Prevention The following relationships exist related to this presentation: The following relationships exist related to this presentation: Pamela N. Peterson MD, MSPH – none Pamela N. Peterson MD, MSPH – none Stacie A. Daugherty MD, MSPH – none Stacie A. Daugherty MD, MSPH – none Yongfei Wang MS – none Yongfei Wang MS – none Humberto J. Vidaillet MD – none Humberto J. Vidaillet MD – none Harlan M. Krumholz MD SM – none Harlan M. Krumholz MD SM – none Paul A. Heidenreich MD – none Paul A. Heidenreich MD – none Jeptha P. Curtis – none Jeptha P. Curtis – none Frederick A. Masoudi – none Frederick A. Masoudi – none

2. Differences in Implantation-Related Adverse Events Between Men and Women Receiving ICD Therapy for Primary Prevention Pamela N Peterson, MD, MSPH Assistant Professor of Medicine Denver Health Medical Center & University of Colorado at Denver and HSC AHA Scientific Sessions November 6, 2007

3. Background Current knowledge of ICD implantation-related adverse events is predicated on clinical trials Current knowledge of ICD implantation-related adverse events is predicated on clinical trials MADIT-II: major complications 2.5% 1 MADIT-II: major complications 2.5% 1 SCD-HeFT: any complications 5.0% 2 SCD-HeFT: any complications 5.0% 2 Little known about complications of ICD implantation in community practice Little known about complications of ICD implantation in community practice Women are at higher risk for adverse events with some invasive cardiac procedures Women are at higher risk for adverse events with some invasive cardiac procedures 12 1 Moss AJ et. al. NEJM 2002;346:877-83. 2 Bardy GH et. al. NEJM 2005;352:225-37.

4. Objectives Determine rates of in-hospital adverse events in patients receiving ICDs for primary prevention in community practice Determine rates of in-hospital adverse events in patients receiving ICDs for primary prevention in community practice Compare rates of events between men and women Compare rates of events between men and women

5. NCDR ™ ICD Registry Participation mandated by CMS Participation mandated by CMS Standardized data elements Standardized data elements  Patient demographics and clinical factors  Diagnostic studies  Device information  Provider and hospital factors Adverse events occurring during the implant until the time of discharge Adverse events occurring during the implant until the time of discharge

6. Study Population 59,833 patients in 1107 hospitals undergoing first-time implantation of an ICD for primary prevention 59,833 patients in 1107 hospitals undergoing first-time implantation of an ICD for primary prevention Exclusions Exclusions  History of syncope  History of cardiac arrest  History of sustained VT  Device revision

7. Outcomes: Major Adverse Events Cardiac arrest Cardiac arrest Cardiac perforation Cardiac perforation Cardiac valve injury Cardiac valve injury Coronary venous dissection Coronary venous dissection Hemothorax Hemothorax Pneumothorax Pneumothorax Deep phlebitis TIA Stroke MI Pericardial tamponade AV Fistula

8. Outcomes: Any Adverse Event Any Major Adverse Event or Any Major Adverse Event or Drug reaction Drug reaction Conduction block Conduction block Hematoma Hematoma Lead dislodgement Lead dislodgement Peripheral embolus Peripheral embolus Superficial phlebitis Superficial phlebitis Infection related to device Infection related to device

9. Methods Baseline characteristics compared between men and women Baseline characteristics compared between men and women Hierarchical logistic regression to evaluate association between gender and implantation- related adverse events adjusting for: Hierarchical logistic regression to evaluate association between gender and implantation- related adverse events adjusting for: Demographic Demographic Clinical Clinical Procedure Procedure Physician Physician Hospital Hospital Stratification by age and device type Stratification by age and device type

10. Population Characteristics MenWomenP-value Age: mean (SD) 68.2 (12.2) 67.6 (12.8) <0.001 Race White White Black Black Hispanic Hispanic83%11%6%77%18%5%<0.001 Diabetes37%39%0.001 Chronic Lung Disease 21%22%0.003 Hypertension73%72%<0.001 Cerebrovascular Disease 14%13%0.005 Renal Failure (dialysis) 4%3%0.023

11. Cardiovascular Characteristics MenWomenP-value History of Heart Failure 83%88%<0.001 NYHA Class Class I Class I Class II Class II Class III Class III Class IV Class IV10%35%50%5%7%30%57%6%<0.001 Ischemic Heart Disease 72%51%<0.001 Non-ischemic Cardiomyopathy 28%47%<0.001 Ejection Fraction: mean (SD) 24.9 (7.7) 24.8 (8.4) 0.255 Bi-Ventricular Pacer/ICD 39%46%<0.001

12. Rates of Adverse Events 3.9% 1.3%

13. Adverse Events More Common in Women P<0.001 3.6%4.8% 1.1% 2.0% 3.9% 1.3%

14. Gender Independently Associated with Adverse Events Unadjusted HR (95% CI) Adjusted Any Adverse Event 1.35 (1.24-1.47) 1.29 (1.19-1.41) Major Adverse Event 1.83 (1.62-2.07) 1.69 (1.48-1.92)

15. Women’s Risk of Major Adverse Events Higher in Subgroups Device Type ICD Bi-V ICD Age <65 >65 1.01.21.41.6 1.8 2.0 1.62 (1.36-1.93) 1.81 (1.55-2.13) 1.48 (1.23-1.77) 1.79 (1.54-2.07)

16. Conclusions In-hospital adverse event rates in community practice are comparable to rates observed in clinical trials In-hospital adverse event rates in community practice are comparable to rates observed in clinical trials In hospital adverse event rates are significantly higher in women than men In hospital adverse event rates are significantly higher in women than men

17. Limitations Adverse events self reported by hospitals Adverse events self reported by hospitals Only short-term adverse events were evaluated Only short-term adverse events were evaluated Unable to determine why adverse event rates were higher in women Unable to determine why adverse event rates were higher in women

18. Implications These results should not preclude women from receiving ICDs These results should not preclude women from receiving ICDs However, the reasons for higher adverse event rates should be investigated and, where possible, eliminated However, the reasons for higher adverse event rates should be investigated and, where possible, eliminated NCDR and other large registries are valuable means of assessing adverse effects of treatment NCDR and other large registries are valuable means of assessing adverse effects of treatment