Anil Verma, MD, Jalal Ghali, MD, Alessandra Meris, MD, J. Malcolm O. Arnold, MD, Mikhail Bourgoun, MD, Eric Velazquez,

1. Prognostic Implications of Left Ventricular Mass and Geometry Following Myocardial Infarction: the VALsartan In Acute myocardial iNfarcTion (VALIANT) Echocardiographic Study

2. Prognostic Implications of Left Ventricular Mass and Geometry Following Myocardial Infarction: the VALsartan In Acute myocardial iNfarcTion (VALIANT) Echocardiographic Study Anil Verma, MD, Jalal Ghali, MD, Alessandra Meris, MD, J. Malcolm O. Arnold, MD, Mikhail Bourgoun, MD, Eric Velazquez, MD, Lars Kober, MD, Marc A. Pfeffer, MD, PhD, Scott D. Solomon, MD Brigham and Women’s Hospital, Wayne State University, University Hospital, LHSC, Duke Clinical Research Institute, Duke University Medical Center, Rigshospitalet, University of Copenhagen

3. BACKGROUND • Left ventricular hypertrophy (LVH) and alterations in LV geometry have been associated with increased mortality and other cardiovascular (CV) events • Patients with concentric LVH (increased relative wall thickness [RWT] and LV mass index [LVMi]), have been shown to have the highest incidence of adverse CV events, including death • There are limited data on the association of LV mass and geometry to prognosis in high risk individuals following myocardial infarction

4. OBJECTIVE To explore the prognostic value of echocardiographically determined LV mass and geometry in the specific setting of high risk MI

5. METHODS double-blind active-controlled 14,703 Valsartan and Captopril Valsartan Captopril • median duration: 24.7 months • event-driven 610 (Echo cohort) 603 (available for analysis)

6. SWTd LVIDd PWTd METHODS • The ASE-recommended formula for estimation of LV mass from 2D linear LV measurements LV mass = 0.8 x {1.04[(LVIDd + PWTd + SWTd)3 - (LVIDd)3]} + 0.6 g • LV mass was indexed to body surface area RWT = 2 x PWTd/LVIDd Devereux RB, Alonso DR, Lutas EM, et al. Echocardiographic assessment of left ventricular hypertrophy: comparison to necropsy findings. Am J Cardiol 1986;57:450–8

7. METHODS Concentric Remodeling N=110 (18%) Concentric Hypertrophy N=76 (13%) Concentric Remodeling N=110 (18%) Concentric Hypertrophy N=76 (13%) ≤0.42 >0.42 Relative Wall Thickness Eccentric Hypertrophy N=112 (19%) Normal Geometry N=305 (51%) Normal Geometry N=305 (51%) Eccentric Hypertrophy N=112 (19%) ≤ 95 (♀) > 95 (♀) ≤ 115 (♂) > 115 (♂) Left Ventricular Mass Index (gm/m2) Lang RM, Bierig M, Devereux RB, et al. Recommendations for chamber quantification. J Am Soc Echo. 2005 Dec;18(12):1440-63

8. Distribution of Baseline LV-Mass index in VALIANT 12 10 Mean LVMi 98.8 ± 28.4 8 Percent of patients 6 4 2 0 0 25 50 75 100 125 150 175 200 225 LV-Mass index gm/m2

9. Baseline characteristics stratified by LV Geometry *p value <0.001 vs. patients with normal LV geometry; Plus-minus values are means ± SD

10. Baseline Echo Characteristics Stratified by LV Geometry Plus-minus values are means ±SD, *p value <0.001; ‡p value <0.01; †p value <0.05 vs. patients with normal geometry *p value <0.001; ‡p value <0.01; †p value <0.05 vs. patients with normal LV geometry

11. Unadjusted Kaplan Meier Curves for All Cause Mortality 0.80 Concentric Hypertrophy 0.60 Cumulative incidence Eccentric Hypertrophy 0.40 Concentric Remodeling 0.20 Normal 0.00 0 200 400 600 800 1000 Days

12. 1.00 0.75 0.50 0.25 0.00 0 200 400 600 800 1000 Days Unadjusted Kaplan Meier curves for Death or Heart Failure Concentric Hypertrophy Eccentric Hypertrophy Cumulative incidence Concentric Remodeling Normal

13. Unadjusted Kaplan Meier Curves for Cardiovascular Composite 1.00 Concentric Hypertrophy 0.80 0.60 Eccentric Hypertrophy CumulativeIncidence Concentric Remodeling 0.40 Normal 0.20 0.00 0 200 400 600 800 1000 Days

14. Adjusted hazard ratios (95%, CI) for adverse outcomes for every 10 gm/m2 increase in baseline LV Mass index and for every 0.1 unit increase in baseline RWT Death/HF Death/HF 1.80 (1.5-2.2) 1.26 (1.2-1.3) CV Death 1.20 (1.1-1.3) CV Death 1.70 (1.3-2.2) CV Composite 1.22 (1.2-1.3) CV Composite 1.60 (1.3-1.9) Death 1.70 (1.3-2.2) 1.19 (1.1-1.3) Death 0.1 unit increase in baseline RWT 0.8 0.9 1.0 1.1 1.2 1.3 1.4 1.5 3.0 0.5 1.0 1.5 2.0 2.5 10 gm/m2 increase in baseline LVMi HR adjusted for age, PTCA for index-MI, afib complicating MI, diabetes, hypertension, prior MI, Killip class, history of CHF, new LBB, history of angina, LVEF, eGFR and COPD

15. Crude incidence rates/100-person years of adverse CV outcomes stratified by LV geometric patterns 100 * 90 * p<0.001 Normal 80 Concentric remodeling † p<0.01 70 Eccentric hypertrophy * 60 Concentric hypertrophy Incidence Rate/100-person years 50 40 * 30 † 20 * † 10 0 HF Stroke SD CV composite CV Death Reinfarction

16. LIMITATIONS • 2D Echo is limited in its accuracy for measuring LV mass since all methods assume a uniform thickness of the LV, which is not the case in areas of chronic infarction or with geometric deformity of the LV cavity • We did not assess for changes in LV mass and its geometrical patterns and its potential influence on CV risk • Finally, our results are predominantly applicable to the high risk post MI patients and generalizability to the broader group of post MI patients may be limited

17. CONCLUSIONS • Echo determined LV geometry and baseline LV mass are important independent predictors of increased morbidity and mortality following MI • Concentric LVH carries the greatest risk of adverse CV events including death • Increase in baseline RWT and the presence of concentric remodeling in the absence of increased LV mass was associated with an increased risk of subsequent CV complications • Our findings suggest that routine assessment of LV mass and RWT could be utilized to better risk-stratify patients following myocardial infarction