1. All Rights Reserved, Duke Medicine 2008 Mechanical Dyssynchrony Defined by Phase Analysis from GSPECT: Does It Predict Mortality? Paul L. Hess, MD; Linda K. Shaw, MS; Robert Clare, MS; Mary L. Shepherd, CNMT; Michael MacKenzie, MS; Robert Pagnanelli, BSRT, CNMT, NCT; Mona Fiuzat, PharmD; Jonathan P. Piccini, MD, MHS; Sana M. Al-Khatib, MD, MHS; Christopher M. O’Connor, MD; and Salvador Borges-Neto, MD

2. All Rights Reserved, Duke Medicine 2008 Cardiac Resynchronization Therapy (CRT) Selection criteria –Reduced ejection fraction (< 35%) –New York Heart Association Class I-IV –QRS duration > 120 ms One third of recipients do not benefit.

3. All Rights Reserved, Duke Medicine 2008 Phase Analysis by GSPECT MPI Standard deviation Bandwidth Dyssynchrony measures Chen J et al. Assessment of Left Ventricular Mechanical Dyssynchrony by Phase Analysis of ECG-gated SPECT Myocardial Perfusion Imaging. J Nucl Cardiol 2008; 15: 127-36.

4. All Rights Reserved, Duke Medicine 2008 Prevalence of Dyssynchrony by GSPECT MPI Samad Z et al. Prevalence and Predictors of Mechanical Dyssynchrony as Defined by Phase Analysis in Patients with Left Ventricular Dysfunction Undergoing Gated SPECT Myocardial Perfusion Imaging. J Nucl Cardiol 2011; 18: 24-30. 39% 71% 31% 56% 52%

5. All Rights Reserved, Duke Medicine 2008 Objective To determine whether mechanical dyssynchrony detected by phase analysis of GSPECT MPI can identify patients with coronary disease at increased risk of all-cause mortality and/or cardiovascular mortality.

6. All Rights Reserved, Duke Medicine 2008 Data Source Duke Databank for Cardiovascular Disease Study Population (n=1,434) Stress testing Angiographically significant coronary disease GSPECT MPI between July 2003 and August 2009 Exercise treadmill testing was preferred

7. All Rights Reserved, Duke Medicine 2008 Emory Toolbox Software (Atlanta, GA) programs were used to assess mechanical dyssynchrony Dyssynchrony Measurement Statistical Analysis Cox proportional hazards modeling Kaplan-Meier survival analysis Unadjusted Adjusted for standard clinical covariates Adjusted for above and LV function

8. All Rights Reserved, Duke Medicine 2008 Age, median (IQR)64 (55, 72) Male sex69.6 Race White73.8 Black22.2 Other4.0 Congestive heart failure24.3 Diabetes mellitus36.2 Hypertension76.1 Hyperlipidemia69.7 COPD6.6 Renal disease5.4 Baseline Characteristics (n=1,434)* *Data are presented as % unless otherwise specified.

9. All Rights Reserved, Duke Medicine 2008 Outcomes Associated with Bandwidth* *Per 10° increment †Adjusted for age, sex, race, chronic obstructive pulmonary disease, diabetes mellitus, hypertension, peripheral vascular disease, cerebrovascular disease, prior myocardial infarction, congestive heart failure, renal insufficiency, and tobacco use ‡Adjusted for above and left ventricular ejection fraction All-cause MortalityPCardiovascular MortalityP Unadjusted1.06 (1.05, 1.08)<0.0011.08 (1.06-1.10)<0.001 Clinical Model†1.06 (1.04, 1.07)<0.0011.07 (1.05-1.09)<0.001 Clinical Model + EF‡1.02 (1.00-1.04)0.1201.02 (1.00-1.05)0.093

10. All Rights Reserved, Duke Medicine 2008 Outcomes Associated with Phase SD* *Per 10° increment †Adjusted for age, sex, race, chronic obstructive pulmonary disease, diabetes mellitus, hypertension, peripheral vascular disease, cerebrovascular disease, prior myocardial infarction, congestive heart failure, renal insufficiency, and tobacco use ‡Adjusted for above and left ventricular ejection fraction All-cause MortalityPCardiovascular MortalityP Unadjusted1.21 (1.16, 1.27)<0.0011.30 (1.23-1.38)<0.001 Clinical Model†1.19 (1.14, 1.25)<0.0011.23 (1.16-1.31)<0.001 Clinical Model + EF‡1.06 (0.99-1.13)0.1011.06 (0.98-1.16)0.158

11. All Rights Reserved, Duke Medicine 2008 Outcomes Associated with Bandwidth By LVEF* Outcome†Left Ventricular FunctionHR (95% CI)Interaction P All-cause mortalityEF > 35%1.06 (1.04-1.07)0.002 EF < 35%0.97 (0.93-1.02) Cardiovascular MortalityEF > 35%1.07 (1.05-1.09)0.002 EF < 35%0.99 (0.93-1.05) *Per 10° increment †Adjusted for age, sex, race, chronic obstructive pulmonary disease, diabetes mellitus, hypertension, peripheral vascular disease, cerebrovascular disease, prior myocardial infarction, congestive heart failure, renal insufficiency, tobacco use, and left ventricular ejection fraction.

12. All Rights Reserved, Duke Medicine 2008 All-Cause Death Over Time Stratified by Left Ventricular Function and Bandwidth Proportion dead Years P=0.604 P<0.001 EF 100 EF < 35%, BW < 100 EF > 35%, BW > 100 EF > 35%, BW < 100

13. All Rights Reserved, Duke Medicine 2008 Cardiovascular Death Over Time Stratified by Left Ventricular Function and Bandwidth Proportion dead Years EF 100 EF < 35%, BW < 100 EF > 35%, BW > 100 EF > 35%, BW < 100 P=0.783 P<0.001

14. All Rights Reserved, Duke Medicine 2008 Implication Patients with LVEF > 35% who do not meet current criteria for CRT may nonetheless benefit from device placement. Principal Finding Mechanical dyssynchrony detected by GSPECT MPI is an early marker of all-cause and cardiovascular mortality among patients with LVEF >35%.

15. All Rights Reserved, Duke Medicine 2008 Limitations Limited number of patients with reduced EF Retrospective, observational study design Sampling bias Diagnostic bias Presence of LBBB unknown

16. All Rights Reserved, Duke Medicine 2008 Conclusions Mechanical dyssynchrony detected by phase analysis of GSPECT MPI can identify patients with coronary disease at increased risk of all- cause mortality and/or cardiovascular mortality after adjustment for standard clinical covariates exclusive of left ventricular ejection fraction. Phase bandwidth is associated with adverse outcomes among patients with LVEF > 35%.