A patient with aortic stenosis and LV dysfunction EuroECHO & Other Imaging Modalities 2012 Athens, Greece

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1 A patient with aortic stenosis and LV dysfunction EuroECHO & Other Imaging Modalities 2012 Athens, Greece Jean-Luc MONIN, MD, PhD. University Hospital, Créteil, FRANCE

2 My disclosures: Lecture and/ or consulting fees from: Abbott Vascular, AstraZeneca, Daiichi-Sankyo, GE Healthcare, Ipsen Pharma, Medtronic CoreValve, MSD, Saint-Jude Medical, Sanofi-Aventis, Servier, Siemens, Toshiba. 2

3 What kind of LV dysfunction? 1. Low EF: Pseudo-severe AS = moderate AS with intrinsic myocardial dysfunction 2. Low EF: True-severe AS = LV systolic dysfunction due to afterload mismatch 3. Preserved EF: Paradoxical low-flow/ lowgradient AS due (in part) to longitudinal LV dysfunction 3

4 What kind of LV dysfunction? 1. Low EF: Pseudo-severe AS = moderate AS with intrinsic myocardial dysfunction 2. Low EF: True-severe AS = LV systolic dysfunction due to afterload mismatch 3. Preserved EF: Paradoxical low-flow/ lowgradient AS due (in part) to longitudinal LV dysfunction 4

5 Male patient, 57 years old NYHA Class III, systolic ejection murmur 5

6 Low LVEF/ High filing pressures 6 LVEF = 25% (Biplane Simpson) E/A > 2

7 Cardiac index = 1.8 L/min/m 2 7

8 MPG = 21 mm Hg / AVA = 0.8 cm 2 : Low-flow/ Low-gradient with low LVEF 8

9 Aortic stenosis in patients with LV systolic dysfunction (Low EF) How to differentiate True-severe from pseudosevere AS? Outcome implications regarding pseudo-severe AS Current role of risk stratification 9

10 Aortic stenosis in patients with LV systolic dysfunction (Low EF) How to differentiate True-severe from pseudosevere AS? Outcome implications regarding pseudo-severe AS Current role role of risk stratification 10

11 defilippi et al. Am J Cardiol. 1995;75: 191-4

12 Dobutamine challenge to assess the real severity of Aortic Stenosis (n= 18) C. Reserve Gradient AVA True severe (n=7) Yes Pseudo severe (n=5) Yes Unresolved (n=6) No? What about patients without contractile reserve? 12 defilippi et al. Am J. Cardiol. 1995; 75: 191-4

13 Projected aortic valve area (TOPAS multicenter Group) 46 consecutive patients ( , Canada/ Austria) AVA 1.2 cm² / LVEF 40% / MPG <40 mm Hg The slope of the regression line of AVA plotted against flow Projected Valve Area : AVA at a standard flow rate of 250 ml/s In 23 operated patients: Fairly concordant with surgical valve inspection. Limitation: no outcome data 13 Blais et al. Circulation. 2006;113:

14 Simplified Projected aortic valve area (TOPAS multicenter Group) 142 consecutive patients ( , Canada/ Austria/ Germany) AVA 1.2 cm² / LVEF 40% / MPG <40 mm Hg Simplified method: the slope of the regression line estimated by dividing the change in AVA from baseline to the peak Dobutamine by the change in cardiac output 14 Clavel et al. J Am Soc Echocardiogr. 2010;23: 380-6

15 Simplified Projected aortic valve area (TOPAS multicenter Group) 142 consecutive patients ( , Canada/ Austria/ Germany) AVA 1.2 cm² / LVEF 40% / MPG <40 mm Hg Both conventional and simplified AVA-proj correlated with excised aortic valve weight (r =0.52 and r = 0.58, respectively) Traditional Dobutaminestress Echo indices did not. 15 Clavel et al. J Am Soc Echocardiogr. 2010;23: 380-6

calcified aortic valve; excepted for some cases of rheumatic AS

16 Over-simplified method : Look at the Valve! In most patients, severe AS is associated with a severely calcified aortic valve; excepted for some cases of rheumatic AS 16 Rosenhek et al. N Engl J Med. 2000;343: Catherine M. otto. N Engl J Med. 2008;359:

17 Measurement of aortic valve calcification by MSCT / Implications for low EF Patients (n= 228) with mild to severe AS underwent prospectively within 1 week Multi Slice Computed Tomography (MSCT) and TTE. In 179 patients with EF >40% (validation set), the best cutoff of AVC for the diagnosis of severe AS was 1651 arbitrary Units. 17 Valve Area < 1 cm 2 Peak aortic-jet velocity > 4 m/s Cueff et al. Heart. 2011;97: 721-6

Measurement of aortic valve calcification by MSCT / Implications for low EF Among patients with low EF (<40%), this cutoff differentiated severe from moderate AS in all but 3 cases 18 MSCT should

18 Measurement of aortic valve calcification by MSCT / Implications for low EF Among patients with low EF (<40%), this cutoff differentiated severe from moderate AS in all but 3 cases 18 MSCT should be considered as an additional tool for the evaluation of AS severity in difficult cases such as patients with difficult Echocardiography or depressed LV function Cueff et al. Heart. 2011;97: 721-6

19 Aortic stenosis in patients with LV systolic dysfunction (Low EF) How to differentiate True-severe from pseudosevere AS? Outcome implications regarding pseudo-severe AS Current role role of risk stratification 19

3 cm²; final EOA>1 cm² Final EOA >1.2 cm²; final MPG <30 mm Hg Δ EOA>0.

20 Pseudo severe aortic stenosis : Prevalence / Prognostic implications Author (year) Definition of Incidence Follow- Mortality Pseudo-severe AS up(months) defilipi (1995) Δ EOA>0.3 cm² 5/18 (28%) 12 20% Schwammenthal (2001) Nishimura (2002) Monin (2003) Δ EOA>0.3 cm²; final EOA>1 cm² Final EOA >1.2 cm²; final MPG <30 mm Hg Δ EOA>0.3 cm²; final EOA >1 cm² 8/24 (30%) 11 25% 7/32 (22%) % 7/136 (5%) 19 50% Zuppiroli (2003) Δ EOA>0.25 cm² 10/48 (21%) 24 70% Pooled 37/258 (14%) % 20 Bermejo & Yotti. Heart. 2007;93:

21 Assessing AS in patients with LV systolic dysfunction: Major issues 1/ Valve calcification («Look at the valve») 2/ LV contractile reserve: perhaps most important, rather than precise distinction between fixed and pseudo-as 3/ Pseudo-severe AS: remains to be tested in large groups, against clinical outcome 21 Paul A. Grayburn Circulation. 2006;113:

22 Clinical outcomes in pseudo severe AS : TOPAS multicenter Group Multicenter study : 101 consecutive patients with Low-gradient AS : AVA 1.2 cm 2, LVEF 40%, MPG 40 mm Hg Projected AVA is an independent predictor of survival in patients treated conservatively 22 Clavel et al. Circulation. 2008; 118; S234-S242

23 Outcomes of pseudo severe AS under conservative treatment (European registry) Outcomes of 107 patients with Low-flow/ low-gradient AS under conservative treatment > 6 months (AVA 1.0 cm 2, LVEF 40%, MPG 40 mm Hg) 23 Fougères et al. Eur Heart J. 2012; 33:

24 Outcomes of pseudo severe AS under conservative treatment (European registry) 1/ The rate of death within 5 years was significantly lower in Pseudo-severe AS(43+11%) as compared with True-severe AS (91+6%, p<0.001) and patients without LV contractile reserve (100%, p<0.001). 24 Fougères et al. Eur Heart J. 2012; 33:

25 Outcomes of pseudo severe AS under conservative treatment (European registry) 2/ Hazard ratio for death remained significantly lower in Pseudo-severe AS after adjustment for currently established risk factors (Independent predictor for survival) 25 Fougères et al. Eur Heart J. 2012; 33:

26 Outcomes of pseudo severe AS under conservative treatment (European registry) 3/ The 5-year survival of pseudo-severe AS patients was comparable with that of propensity-matched patients (n=28) with systolic heart failure and no evidence of valve disease These results provide direct evidence that the distinction between pseudo-severe and true-severe AS is clinically relevant in the setting of Lowflow/ Low-ejection fraction. Further studies are needed to define optimal therapeutic management in these patients. 26 Fougères et al. Eur Heart J. 2012; 33:

27 Aortic stenosis in patients with LV systolic dysfunction (Low EF) How to differentiate True-severe from pseudosevere AS? Outcome implications regarding pseudo-severe AS Current role role of risk stratification 27

$Low-gradient/ Low-ejection fraction AS: predictors of postoperative outcome 217 consecutive patients (77% men) with$

28 Low-gradient/ Low-ejection fraction AS: predictors of postoperative outcome 217 consecutive patients (77% men) with severe AS, LVEF <35% and MPG <30 mm Hg, who underwent AVR between 1990 and Levy et al. J Am Coll cardiol. 2008;51: 1472

$Low-gradient/ Low-ejection fraction AS: predictors of$ powerful predictor for perioperative mortality Predictors of

29 Low-gradient/ Low-ejection fraction AS: predictors of postoperative outcome LV contractile reserve remains a powerful predictor for perioperative mortality Predictors of perioperative mortality 29 Levy et al. J Am Coll cardiol. 2008;51: 1472

30 Therapeutic options in AS: Current role of risk stratification 30

31 Take-Home Messages : AS with low-flow/ low-gradient/low-ef 31 Pseudo-severe AS refers to moderate AS with primary (intrinsic) myocardial dysfunction It can be identified by Dobutamine Echo (AVA or projected AVA > 1.2 cm 2 ) or the assessment of AV calcification (visual estimate or MSCT) Although further studies are needed, valve intervention may not be required in Pseudo-severe AS True-severe AS: LV systolic dysfunction due to afterload mismatch; valve intervention probably beneficial in most cases ESC/ EACTS: in the TAVI era, patient s management still relies on risk stratification, including Dobutamine Echo

AS with reduced LV ejection fraction: Contractile reserve should be systematically assessed: PRO

$AS with reduced LV ejection fraction: Contractile reserve should be systematically assessed: PRO$ AS with reduced LV ejection fraction: Contractile reserve should be systematically assessed: PRO Jean-Luc MONIN, MD, PhD Henri Mondor University Hospital Créteil, FRANCE Potential conflicts of interest