1. Evaluation and Management of Asymptomatic Aortic Stenosis. Augusto Pichard, M.D. Director Innovation and Structural Heart Disease, Vice Chair, Medstar Heart Institute, Medstar Washington Hospital Center. Professor of Medicine (Cardiology), Georgetown University Medical School. Washington, DC Snowmass 2014

2. Symptoms of Aortic Stenosis Main symptoms: –dyspnea, –angina, –syncope, Other important symptoms: –dizziness, –weakness, –fatigue, –exercise intolerance. Patients may not be aware of symptoms.

3. Asymptomatic Aortic Stenosis Main Message: Asymptomatic severe AS is not a benign condition. Patients with asymptomatic severe AS may need AVR before symptoms are manifest.

4. Mortality of Asymptomatic Severe Aortic Stenosis

5. Incidence of Sudden Death in Asymptomatic Aortic Stenosis Rahimtoola EHJ 2008; 29:1783-91. Lancelotti AJC 2010 1264.8

6. Patients n= 26 128 66 69 125 622 Rahimtoola, EHJ 08

7. Outcome of Asymptomatic Aortic Stenosis Pellikka et al. Circulation 2005;111:3290-5 During 5 year follow up: 57% had AVR 43% died (19% cardiac death). Sudden death without preceding symptoms occurred in 4.1% of 270 unoperated patients 622 patients with peak veloc >4m/sec, AVA 0.9±0.2cm2 2 y 5 y

8. Predictors of events

9. Aortic Jet Velocity and Survival. Otto et al. Circulation 1997, 95:2262 20% events at 5 years 40% events at 4 years 80% events at 3 years 100% events at 5 years 123 AS patients without symptoms

10. Jet Velocity, AVA and Outcome Otto et al. Circulation 1997, 95:2262 AVA cm2 Ao Jet Veloc. m/sec

11. Jet Velocity Progression and Outcome in Severe Asymptomatic Aortic Stenosis Rosenhek et al. NEJM 2000; 343:611-7 Mean Rate of Progression of Aortic-Jet Velocity among 41 Patients with and 29 patients without Cardiac Events 34 Patients with Moderate or Severe Calcification of the Aortic Valve and a Rapid Increase in Aortic-Jet Velocity (at Least 0.3 m/sec within 1 Year). >0.3 m/sec/year

12. Valve Calcification is a Predictor of Outcome in Severe Asymptomatic AS Rosenhek et al. NEJM 2000; 343:611-7 Calcification by CT predicts outcome in asymptomatic AS. J Heart Valve Dis 2007;15:494

13. Exercise Test is indicated in Asymptomatic Aortic Stenosis

14. Exercise testing in Asymptomatic AS Amato et al. Heart 2001; 86:381-6 Although asymptomatic in daily life, 6% of the patients (4/66) experienced sudden death: all with positive exercise test and aortic valve area 0.6 cm2.

15. Incremental Prognostic Value of Exercise Test Lancelotti et al. Circul 2005;112:I 377-82 Predictive value

16. AHA/ACC Guidelines for AVR Circulation, ahead of Print March 2014 New in 2014: AVR indicated in patients with Asymptomatic Severe AS and exercise testing showing: decreased exercise tolerance drop in BP during treadmill testing

17. Other Predictors of events

18. ECG in Asymptomatic AS Greve, Wachtell et al. Copenhagen.

19. Exhausted Coronary Flow Reserve in AS Pichard, Gorlin et al. Am J Cardiol 1981;47: 547-54 As LV Mass increases, coronary flow needs to augment. In severe AS, resting coronary flow is high and flow reserve is exhausted. These patients have ischemia during exercise. LVH with “strain” on ECG may be a sign of exhausted CFR and underlying ischemia at rest. Rapid clinical deterioration may follow after this threshold of CBF is reached.

20. LA Size and Survival in Asymptomatic Severe AS Casaglang-Verzos, Pellika et al. Echocardiography 2010;27:105-9 Diastolic function, evaluated by LA size, determines Mortality independent of age, gender, AS severity, and Doppler diastolic function.

21. Survival of Asymptomatic AS According to Score. Monin et al. Circulation 2009;120:69-75 Independent predictors used in Score: female sex, peak aortic-jet velocity, and BNP at baseline. n=214 pts.

22. BNP and Tissue Doppler in Asymptomatic AS. Rajani et al. J Heart Valve Dis 2009;18:565-571 65 asymptomatic patients with AVA 0.8-1.2 cm2 Patients with BNP < 58 have no symptoms for the next 12 months. 88% of patients with BNP >250, and 50% of patients with BNP >58 developed symptoms within 1 year.

23. Valvulo-Arterial Impedance in Asymptomatic AS Hachicha et al. Laval Univ. JACC 2009;54;1003-1011 544 patients with moderate or severe AS mmHg/ml/m 2 Z VA = SAP+MG SVi

24. Low Flow, Low Gradient Asymptomatic AS Cramariuc et al. JACC imaging 2009;2:390-9 1873 asymptomatic AS patients from the SEAS Study. 28% had severely reduced energy loss index and: - more concentric LVH. - smaller LV cavity (normal EF). - increased valvulo-arterial impedance. - decreased stress corrected midwall shortening. - decreased survival.

25. Excessive LV Mass and Outcome Rahimtoola EHJ 2008;29:1783-90 Some patients have more LVH than appropriate for the degree of AS (>12-14 mm in women and > 14-16mm in men, with high EF). Occurs more often in women. These patients have higher surgical mortality and persistent symptoms of diastolic dysfunction after surgery. These patients should have surgery early.

26. Summary of Predictors Pts with severe AS and no symptoms are at higher risk of events if: Symptoms during exercise test. AVA <1.0 cm2 Jet velocity >4 m/sec Increase in jet velocity >.3 m/s x year Severe valve calcification Disproportionate LVH Elevated BNP, elevated Zva, etc.

27. Why Operate Early ? Severe AS, even asymptomatic, has Very low surgical mortality/morbidity. Higher surgical mortality when more symptomatic.

28. Surgery for Asymptomatic Severe AS. Kand, Park et al. Circulation 2010;121:1502-9 n=197

29. AVR in USA 1999-2011 Barretto-Filha et al. JAMA 2013;310:2078-84 20012011 # Patients26,59831,380 30 day Mortality 7.34.2 Age 65-745.73.3 Age 75-847.84.4 Age > 8510.85.8

30. 1993-2003 Loma Linda Echo Lab Database. Pai et al. Ann Thor Surg 2006;82:2116-22 Asymptomatic Patients Valve Replacement No surgery 338 asymptomatic patients with AVA <0.8 cm2

31. AVR in the Elderly. Cerillo et al. Interact CardioVasc Thorac Surg 2007;6:308-13

32. Conclusions Severe AS is a serious condition associated with high mortality. Some patients “report” no symptoms in spite of significant limitations. Follow these patients with yearly exercise echo-doppler. All patients with severe AS should be evaluated for possible AVR, independent of symptoms.

33. The end

34. P<0.001 4.1 5.3 NF PLF Global LV Hemodynamic Load: Valvulo-Arterial Impedance (Z va ) Hachicha Z et al., Circ 2007; 115:2856-64 (mmHg/ml/m 2 ) Z VA = SAP+MG SVi Briand, JACC, 46:291-296,2005

35. Mortality for AVR. STS Executive Summary 2008 www.sts.org 10