1. Clinical Trial Results. org Impact of Epicardial Anterior Fat Pad Retention on Postcardiothoracic Surgery Atrial Fibrillation Incidence: The AFIST-III Study C. Michael White, PharmD; Stephen Sander, PharmD; Craig I. Coleman, PharmD; Robert Gallagher, MD; Hiroyoshi Takata, MD; Chester Humphrey, MD; Nickole Henyan, PharmD; Effie L. Gillespie, PharmD; Jeffrey Kluger, MD Published in the Journal of the American College of Cardiology January 23, 2007 Impact of Epicardial Anterior Fat Pad Retention on Postcardiothoracic Surgery Atrial Fibrillation Incidence: The AFIST-III Study C. Michael White, PharmD; Stephen Sander, PharmD; Craig I. Coleman, PharmD; Robert Gallagher, MD; Hiroyoshi Takata, MD; Chester Humphrey, MD; Nickole Henyan, PharmD; Effie L. Gillespie, PharmD; Jeffrey Kluger, MD Published in the Journal of the American College of Cardiology January 23, 2007

2. Clinical Trial Results. org Drugs with antiadrenergic effects reduce postoperative atrial fibrillation (POAF).Drugs with antiadrenergic effects reduce postoperative atrial fibrillation (POAF). Because the epicardial anterior fat pad (AFP) is parasympathetically innervated, its routine excision during coronary artery bypass grafting (CABG) may precipitate autonomic imbalance and induce POAF.Because the epicardial anterior fat pad (AFP) is parasympathetically innervated, its routine excision during coronary artery bypass grafting (CABG) may precipitate autonomic imbalance and induce POAF. Drugs with antiadrenergic effects reduce postoperative atrial fibrillation (POAF).Drugs with antiadrenergic effects reduce postoperative atrial fibrillation (POAF). Because the epicardial anterior fat pad (AFP) is parasympathetically innervated, its routine excision during coronary artery bypass grafting (CABG) may precipitate autonomic imbalance and induce POAF.Because the epicardial anterior fat pad (AFP) is parasympathetically innervated, its routine excision during coronary artery bypass grafting (CABG) may precipitate autonomic imbalance and induce POAF. The AFIST-III Study: Background White et al., JACC 2007; 49(3): 298-303

3. Clinical Trial Results. org Given conflicting preliminary data, the Atrial Fibrillation Suppression Trial-III (AFIST-III) was conducted to evaluate the impact of maintaining the AFP on POAF.Given conflicting preliminary data, the Atrial Fibrillation Suppression Trial-III (AFIST-III) was conducted to evaluate the impact of maintaining the AFP on POAF. Additionally, the present study evaluated the impact of AFP maintenance on heart rate variability, an established marker of parasympathetic tone, in order to explore the underlying mechanism.Additionally, the present study evaluated the impact of AFP maintenance on heart rate variability, an established marker of parasympathetic tone, in order to explore the underlying mechanism. Given conflicting preliminary data, the Atrial Fibrillation Suppression Trial-III (AFIST-III) was conducted to evaluate the impact of maintaining the AFP on POAF.Given conflicting preliminary data, the Atrial Fibrillation Suppression Trial-III (AFIST-III) was conducted to evaluate the impact of maintaining the AFP on POAF. Additionally, the present study evaluated the impact of AFP maintenance on heart rate variability, an established marker of parasympathetic tone, in order to explore the underlying mechanism.Additionally, the present study evaluated the impact of AFP maintenance on heart rate variability, an established marker of parasympathetic tone, in order to explore the underlying mechanism. The AFIST-III Study: Background White et al., JACC 2007; 49(3): 298-303

4. Clinical Trial Results. org R  Primary Endpoint: Incidence of POAF, total hospital costs  Secondary Endpoint: Heart rate variability, length of hospital stay, and the impact of AFP retention on safety parameters (another arrhythmia, MI, hypotension, bradycardia, mortality, and stroke).  Primary Endpoint: Incidence of POAF, total hospital costs  Secondary Endpoint: Heart rate variability, length of hospital stay, and the impact of AFP retention on safety parameters (another arrhythmia, MI, hypotension, bradycardia, mortality, and stroke). 180 patients undergoing CABG surgery mean age 66 + 10 yrs, 80% male, 5% previous atrial fibrillation Randomized. Blinded. Controlled. Exclusion Criteria: Age < 50 yrs; Atrial Arrhythmia at Enrollment; Previous CABG; Enrolled in Competing Study; Concomitant Valve Replacement or MAZE Procedure; Refusal to Participate 180 patients undergoing CABG surgery mean age 66 + 10 yrs, 80% male, 5% previous atrial fibrillation Randomized. Blinded. Controlled. Exclusion Criteria: Age < 50 yrs; Atrial Arrhythmia at Enrollment; Previous CABG; Enrolled in Competing Study; Concomitant Valve Replacement or MAZE Procedure; Refusal to Participate White et al., JACC 2007; 49(3): 298-303 The AFIST-III Study: Study Design AFP removal (n=88) (n=88) AFP maintenance (n=92) (n=92) 30 day follow-up

5. Clinical Trial Results. org The AFIST-III Study: Study Demographics Characteristic AFP Removed (n=88) AFP Maintained (n=92) p-value History of Atrial Fibrillation (%) 4.54.31.000 History of Smoking (%) 60.272.80.043 Left Ventricular EF (%) 52.6 + 12.3 52.4 + 12.5 0.905 Mitral Regurgitation (%) 19.310.90.135 On-pump surgery (%) 46.654.30.232 Vein Grafts (n) 2.0 + 1.3 2.4 + 1.3 0.059 White et al., JACC 2007; 49(3): 298-303

6. Clinical Trial Results. org Incidence of POAF (%) The AFIST-III Study: Primary Endpoint White et al., JACC 2007; 49(3): 298-303 Difference in the Incidence of POAF between Groups p=0.950 p=0.835 p=0.905 There was no difference in the incidence of POAF, symptomatic POAF, or recurrent POAF between AFP removal and AFP maintenance groupsThere was no difference in the incidence of POAF, symptomatic POAF, or recurrent POAF between AFP removal and AFP maintenance groups

7. Clinical Trial Results. org The AFIST-III Study: Primary Endpoint Total Hospital Costs ($) Difference in Total Hospital Costs between Groups Because POAF was not impacted, there was no significant difference in total hospital costs between the AFP removed and the AFP maintained groupsBecause POAF was not impacted, there was no significant difference in total hospital costs between the AFP removed and the AFP maintained groups White et al., JACC 2007; 49(3): 298-303 p=0.647

8. Clinical Trial Results. org The AFIST-III Study: Secondary Endpoint White et al., JACC 2007; 49(3): 298-303 22.7 + 8.3 31.7 + 24.6 10.1 + 5.5 17.1 + 11.9 p=0.05 p=0.003 Heart rate variability between the two groups Heart Rate Variability Subjects with AFP removal had lower HRV than those with AFP maintenance as determined by both the SDNN (p=0.05) and the SDANN 5 (p=0.003)Subjects with AFP removal had lower HRV than those with AFP maintenance as determined by both the SDNN (p=0.05) and the SDANN 5 (p=0.003)

9. Clinical Trial Results. org The cardiothoracic surgeons were not blinded to study group allocation. However, the impact of not blinding the surgeon was minimized by blinding data collectors, clinicians who treated the patients, and the patients themselves.The cardiothoracic surgeons were not blinded to study group allocation. However, the impact of not blinding the surgeon was minimized by blinding data collectors, clinicians who treated the patients, and the patients themselves. Use of other drugs to control POAF was not controlled for.Use of other drugs to control POAF was not controlled for. The cardiothoracic surgeons were not blinded to study group allocation. However, the impact of not blinding the surgeon was minimized by blinding data collectors, clinicians who treated the patients, and the patients themselves.The cardiothoracic surgeons were not blinded to study group allocation. However, the impact of not blinding the surgeon was minimized by blinding data collectors, clinicians who treated the patients, and the patients themselves. Use of other drugs to control POAF was not controlled for.Use of other drugs to control POAF was not controlled for. The AFIST-III Study: Limitations White et al., JACC 2007; 49(3): 298-303

10. Clinical Trial Results. org AFP maintenance did not positively or negatively impact clinical end points, particularly POAF, in the AFIST-III study.AFP maintenance did not positively or negatively impact clinical end points, particularly POAF, in the AFIST-III study. Maintaining the AFP does not alter the incidence of POAF after CABG or total hospital costs in any appreciable way, even though it preserves parasympathetic tone.Maintaining the AFP does not alter the incidence of POAF after CABG or total hospital costs in any appreciable way, even though it preserves parasympathetic tone. AFP maintenance did not positively or negatively impact clinical end points, particularly POAF, in the AFIST-III study.AFP maintenance did not positively or negatively impact clinical end points, particularly POAF, in the AFIST-III study. Maintaining the AFP does not alter the incidence of POAF after CABG or total hospital costs in any appreciable way, even though it preserves parasympathetic tone.Maintaining the AFP does not alter the incidence of POAF after CABG or total hospital costs in any appreciable way, even though it preserves parasympathetic tone. The AFIST-III Study: Summary White et al., JACC 2007; 49(3): 298-303