1. The Relationship Between Renal Function and Cardiac Structure, Function, and Prognosis Following Myocardial Infarction: The VALIANT Echo Study Anil Verma, MD, Nagesh S. Anavekar, MD, Alessandra Meris, MD, Jens Jakob Thune, MD, J. Malcolm O. Arnold, MD, Jalal K. Ghali, MD, Eric J. Velazquez, MD, John J.V. McMurray, MD, Marc A. Pfeffer, MD, PhD, Scott D. Solomon, MD J Am Coll Cardiol 2007;50:1238-1245

2. Copyright ©2007 American College of Cardiology Foundation. Restrictions may apply. J Am Coll Cardiol 2007;50:1238-1245 Background & Objectives Background: Renal impairment is associated with adverse cardiovascular outcomes post-MI Objectives: To determine whether alterations in cardiac structure or function contribute to the increased risk associated with renal impairment following myocardial infarction (MI)

3. Copyright ©2007 American College of Cardiology Foundation. Restrictions may apply. J Am Coll Cardiol 2007;50:1238-1245Methods Echocardiography was performed on 603 patients with left ventricular (LV) dysfunction, heart failure (HF), or both following MI. Patients were grouped according to their estimated glomerular filtration rate (eGFR), and measures of cardiac structure and function were related to baseline eGFR. The relationship between eGFR, cardiac structure and function, and clinical outcomes of death or heart failure was assessed using multivariable Cox regression.

4. Copyright ©2007 American College of Cardiology Foundation. Restrictions may apply. J Am Coll Cardiol 2007;50:1238-1245 Multivariate Adjustment The adjustment model included predictors of mortality identified from the overall VALIANT study: age (in years), sex, primary percutaneous transluminal coronary angioplasty post-MI, atrial fibrillation complicating MI, history of diabetes, history of hypertension, prior MI, Killip class, and a history of chronic obstructive pulmonary disease. In addition to the above risk factors, adjustment was also made for the echocardiographic variable of interest, with each variable entering separately into the model and treatment assignment. The echocardiographic variables were: LV end systolic volume, LV ejection fraction, left atrial volume index, ratio of mitral regurgitation area to left atrial area, RV fractional area shortening, and LV mass index.

5. Copyright ©2007 American College of Cardiology Foundation. Restrictions may apply. J Am Coll Cardiol 2007;50:1238-1245 105 110 115 120 125 <4545-59.960-74.9≥75.0 eGFR (ml/min/1.73m 2 ) End diastolic volume (ml) p (trend) = 0.02 End Diastolic Volume Decreases as eGFR Declines

6. Copyright ©2007 American College of Cardiology Foundation. Restrictions may apply. J Am Coll Cardiol 2007;50:1238-1245 85 90 95 100 105 110 115 <4545-59.960-74.9≥75.0 eGFR (ml/min/1.73 m 2 ) LV-Mass index (gm/m 2 ) p (trend) <0.001 LV Mass Index Increases as eGFR Decreases

7. Copyright ©2007 American College of Cardiology Foundation. Restrictions may apply. J Am Coll Cardiol 2007;50:1238-1245 1.4 1.5 1.6 1.7 1.8 1.9 <4545-59.960-74.9≥75.0 eGFR (ml/min/1.73 m 2 ) LV-Mass/EDV p (trend) <0.001 Relationship Between eGFR & LV Mass/EDV

8. Copyright ©2007 American College of Cardiology Foundation. Restrictions may apply. J Am Coll Cardiol 2007;50:1238-1245 20 22 24 26 28 30 <4545-59.960-74.9≥75.0 eGFR (ml/min/1.73m 2 ) LA volume index (ml/m 2) p (trend) <0.001 Relationship Between eGFR & LA-volume Index

9. Copyright ©2007 American College of Cardiology Foundation. Restrictions may apply. J Am Coll Cardiol 2007;50:1238-1245 0 10 20 30 40 50 60 70 <4545-59.960-74.9≥75.0 eGFR (ml/min/1.73 m2) Percentage of patients with LVH p<0.001 Left Ventricular Hypertrophy Increases as eGFR Declines

10. Copyright ©2007 American College of Cardiology Foundation. Restrictions may apply. J Am Coll Cardiol 2007;50:1238-1245 eGFR, ml/min/1.73 m 2 P (trend) <4545-59.960-74.9≥75.0 Baseline to 20 months N3078130190 ∆ LAVI, ml/m 2 4.2 ± 9.45.6 ± 8.11.9 ± 6.32.4 ± 6.40.039 ∆ EDV, ml1.8 ± 15.45.0 ± 18.21.7 ± 16.51.8 ± 18.50.25 ∆ ESV, ml-0.07 ± 14.93.0 ± 16.2-1.4 ± 16.11.3 ± 16.90.15 ∆ LVEF, %1.5 ± 7.00.7 ± 6.72.3 ± 7.72.3 ± 7.10.31 Values are presented as mean±SD. EDV = end diastolic volume; ESV = end systolic volume; LVEF = left ventricular ejection fraction; LAVI = left atrial volume index Change in Echocardiographic Measures Stratified by eGFR Group

11. Copyright ©2007 American College of Cardiology Foundation. Restrictions may apply. J Am Coll Cardiol 2007;50:1238-1245 eGFR, ml/min/1.73 m 2 <45.045.0–59.960.0–74.9≥75Overall model χ2 MV2.1 (1.2–2.8); P=0.007 1.8 (1.1–2.8); P=0.015 1.4 (0.9–2.2); P=0.13 1.085.7 MV including ESV2.3 (1.3–4.0); P=0.004 1.8 (1.1–2.9); P=0.017 1.4 (0.9–2.2); P=0.16 1.099.0 MV including LVEF2.1 (1.2–3.7); P=0.007 1.7 (1.1–2.7); P=0.20 1.3 (0.8–2.1); P=0.20 1.0103.6 MV including LAVI2.1 (1.2–3.7); P=0.011 1.7 (1.0–2.7); P=0.045 1.4 (0.8–2.2); P=0.17 1.0110.0 MV including MR jet area/LA area 2.0 (1.1–3.7); P=0.025 1.9 (1.1–3.2); P=0.014 1.4 (0.8–2.3); P=0.19 1.0104.8 MV including LVMI1.6 (0.9–2.9); P=0.08 1.4 (0.9–2.3); P=0.17 1.1 (0.7–1.8); P=0.60 1.0176.1 MV = multivariate; EDV = end diastolic volume; ESV = end systolic volume; LVEF = left ventricular ejection fraction; LAVI = left atrial volume index Hazard Ratios (95% CI) for All-Cause Mortality and/or Hospitalization for Heart Failure Stratified by eGFR Group

12. Copyright ©2007 American College of Cardiology Foundation. Restrictions may apply. J Am Coll Cardiol 2007;50:1238-1245 Conclusion Renal impairment was associated with smaller LV and larger LA volumes and increased LVMI. Systolic function was similar when compared with patients with normal renal function. Thus, reduced systolic function cannot account for worse outcomes in patients with renal impairment post-MI. Indirect measures of diastolic function suggest that diastolic dysfunction may be an important mediator of increased risk in this population.