EuroEcho 2011
Budapest
How to treat an asymptomatic
patient with AVA 0.65 cm²?
Philippe Pibarot, DVM, PhD, FACC, FAHA, FESC
Canada Research Chair in Valvular Heart Diseases
Université
LAVAL
Disclosure

None
Case Study #1: Asymptomatic
Patient with Severe AS
 65 y.o. man with history of calcific AS
 Asymptomatic
 Exercise testing: 11 METS
 No evidence of obstructive CAD
 LVEF: 65%
 AS severity on echo:
0.65 cm2 (1 Yr ago: 0.70)
 Indexed AVA: 0.35 cm2/m2
 Peak jet velocity: 5.1 m/s (1 Yr ago: 4.8 m/s)
 Peak/mean gradient: 104/64 mmHg
(1 Yr ago: 95/58 mmHg)
 AVA:
Case Study #1:
Severe Aortic Valve Calcification
Case study #1:
Clinical dilemna in this patient:

Early « Prophylactic » Surgery?
OR

Watchful waiting?
Severe Aortic Stenosis
VPeak>4 m/s
Mean gradient >40 mm Hg
AVA < 1.0 cm²
Undergoing CABG or
other heart surgery?
Symptoms?
Yes
No
Equivocal
Exercise test
Symptoms
BP
(ESC)
Normal
LV ejection fraction
<50%
(ACC/AHA)
ESC – ACC/AHA Guidelines
Class I
Class I
Class IIb
Class I
Aortic Valve Replacement
Preoperative coronary angiography
Exercise Testing for to Unmask Symptoms in AS
29%
PPV 79% if age <70 y
PPV 45% if age >70 y
Das et al Eur Heart J 2005; 26:1309-13
Case study #1:
Asymptomatic Patient with Severe AS
Clinical dilemna :
 Early
« Prophylactic » Surgery vs. Watchful
Waiting?
 Risk stratification is key:
Step #1: Markers of AS severity a/o rapid stenosis
progression
 Step #2: Impact of the hemodynamic load on the myocardial
structure and function

Relationship between AS Severity
and Coronary Flow Reserve
Garcia et al. J Appl Physiol; 106:113-21, 2009
Natural History of Very Severe AS
Rosenhek et al. Circulation. 2010;121:151-156
Predictors of Outcome in Severe
Asymptomatic AS
Valve Calcification
(≥2/3)
Rapid Stenosis Progression
(≥0.3 m/s/yr)
Rosenhek et al N Engl J Med 2000; 343:611-7
Early Surgery Versus Conventional Treatment
in Asymptomatic Very Severe Aortic Stenosis
Kang et a. Circulation. 2010;121:1502-1509
Severe Aortic Stenosis
VPeak>4 m/s
Mean gradient >40 mm Hg
AVA < 1.0 cm²
Re-evaluation
Undergoing CABG or
other heart surgery?
Symptoms?
Yes
No
Equivocal
Normal
Exercise test
Symptoms
BP
(ESC)
<50%
Normal
(ACC/AHA)
Yes
(ESC)
Class I
Class I
LV ejection fraction
Class IIb
Class I
Aortic Valve Replacement
Preoperative coronary angiography
Class IIa
(ACC/AHA)
Class IIb
Very severe AS
Severe valve calcification
Rapid progression
No
Clinical follow-up, patient education,
risk factor modification, annual echo
Case Study #1
 Very severe stenosis (AVA<0.6 cm2, VPeak>5.5 m/s): NO
 Severe valve calcification (3/3): YES
 Rapid stenosis progression (≥0.3 m/s/yr): YES
Other emerging risk markers?
Exercise-stress echocardiography for
risk stratification in AS
Lancellotti et al.
Circulation 2005;112:I 377-I 382
Exercise-stress echocardiography for risk
stratification in “true asymptomatic” AS
Event-free Survival (%)
100
80
Rest MG≤35
Ex ∆MG>20
HR=1; reference
Rest MG≤35
Ex ∆MG≤20
HR=0.8; p=ns
60
Rest MG>35
Ex ∆MG≤20
40
HR=2.5; p<.001
20
p<0.0001
Rest MG>35
Ex ∆MG>20
0
0
6
12
18
HR=9.6; p<.0001
24
Follow-up (months)
Maréchaux et al, Eur Heart J 2010
Case Study #1:
Exercise-Stress Echo
 No exercise-limiting symptoms
 No fall in blood pressure
 Peak exercise gradients

Peak/mean gradient: 151/103 mmHg (rest 104/64 mmHg)
 Absolute
increase in mean gradient: +39 mmHg
Calcific AS : A Continuum that involves
the Valve, the Vessels and the Ventricle
40% of patients with calcific AS have markedly reduced arterial compliance
Briand et al., JACC, 2005;46:291-8.
Left Ventricular Afterload in Aortic Stenosis =
Valvular Load + Arterial Load
AA
EOA
SV
Static Pressure
LVSP
}
}
∆Pnet
∆P
SAP
}
Valvular Load
Arterial Load
Total Load
Flow axis
Valvulo-Arterial Impedance
Briand et al., JACC,
46:291-8, 2005
Hachicha et al., Circulation,
115:2856-2864, 2007
LVSP
Zva =
SVi
SAP +∆PMean
=
SVi
>3.5: Moderate
>4.5: Severe
Case #1: Zva=5.1
Impact of Valvulo-Arterial Impedance
on Overall Survival
100
Survival
(%)
3 years
Zva<3.5
80
3.5≤Zva<4.5 80 ± 3%
60
544 Pts.
≥ moderate AS
Asymptomatic
Zva≥4.5
70 ± 5%
40
20
General Canadian
Population Matched
for Age-Gender
P < 0.001
0
0
Hachicha et al.
JACC 54;
1003-1011; 2009
88 ± 3%
2
4
6
Follow-up (years)
Adjusted Hazard Ratios:
3.5≤Zva<4.5: : 1.7 (95% CI: 1.4-5.6); p=0.01
Zva≥4.5: 2.0 (95% CI: 1.4-6.6); p=0.006
8
Risk stratification in AS: Importance of valvular,
arterial and ventricular interplay
163 asymptomatic patients with severe AS
Peak aortic velocity ≥ 4.4
HR= 1.7, p=0.027
m.s-1
HR= 1.9, p=0.013
Zva ≥ 4.9 mmHg.ml-1.m-2
HR= 2.2, p=0.003
Longitudinal strain ≤ 15.9 %
HR= 2.8, p=0.001
Ind. LA area ≥ 12.2 cm2/m2
Case #1: GLS=13%
Lancellotti et al. Heart 2010
0
1
2
4
3
Hazard-ratio
5
6
Impact of Cumulative Number of Risk
Factors
Event-free Survival, %
100
p<0.001
80
76±6%
73±10%
73±10%
70±8%
60
Risk Factor =0, (n=20)
Risk Factor =1, (n=56)
Risk Factors =2, (n=57)
40
40±8%
35±8%
20
15±8%
0
0
1
2
Risk Factors ≥3, (n=30)
10±6%
3
4
5
Follow-up, years
6
7
Lancellotti et al. Heart 2010
Risk Score for Predicting Outcome
in Asymptomatic AS



107 pts followed in Créteil
Risk score according to
independent variables
Validation in Liège (107 pts)
ScoreScore
= (Peak
velocity
= (5.2
× 2) × 2)
++(nat
1.5)
(natlog
logBNP
190 ×× 1.5)
+1.5
female)
+1.5(if
(0)=
16.1
> 75%
O bs erv ed 24-month ev ent rates (% )
100
90
80
70
60
50
40
30
20
10
0
< 10%
7
9
11
13
15
17
16
19
21
23
R is k S c ore v alue
Monin, Lancellotti et al. Circulation, 2009
Case Study #1: Asymptomatic
Patient with Severe AS
 65 y.o. man with history of calcific AS
 Asymptomatic
 Exercise testing: 13 METS
 No evidence of obstructive CAD
 LVEF: 65%
 AS severity on echo:
0.65 cm2 (1 Yr ago: 0.70)
 Indexed AVA: 0.35 cm2/m2
 Peak jet velocity: 5.1 m/s (1 Yr ago: 4.8 m/s)
 Peak/mean gradient: 104/64 mmHg
(1 Yr ago: 95/58 mmHg)
 AVA:
Step #1:
Assess Markers of Valve Stenosis Severity
and/or Rapid Stenosis Progression
 Very severe stenosis (AVA<0.6 cm2, VPeak>5.5 m/s): NO
 Severe valve calcification (3/3): YES
 Rapid stenosis progression (≥0.3 m/s/yr): YES
 Marked gradient increase during exercise (>18-20 mmHg): YES
Step #2:
Assess Global LV Hemodynamic Load and
Repercussion on Myocardial Function
 High valvulo-arterial impedance (Zva>4.5) : YES
 Reduced global longitudinal strain (<15%): YES
 Elevated plasma BNP (a/or increase during FU): YES
 Enlarged left atrium: YES
Severe Aortic Stenosis
VPeak>4 m/s, Mean gradient >40 mmHg
EOA <1.0 cm²
Re-evaluation
Undergoing CABG or
other heart surgery?
Symptoms?
Symptoms
BP
Yes
No
Equivocal
Normal
LV ejection fraction <50%
Exercise stress test
[ Very High BNP]
Yes
(ESC)
(ACC/AHA)
Very severe stenosis
Severe valve calcification
Rapid stenosis progression
Large increase in gradient (>18-20 mmHg) on exercise
Yes
(ACC/
AHA)
No
(ESC)
Moderately high BNP
High Zva
Reduced global longitudinal strain
Class I
Class I
Class IIb
Class I
Class IIb
Class IIa
Yes
Aortic Valve Replacement
Preoperative coronary angiography
3-6 Mo clinical, echo
& BNP follow-up
No
Annual clinical, echo
& BNP follow-up
Case Study #2
 78 y.o. female with history of calcific AS
 Mild hypertension
 No evidence of obstructive CAD
 LVEF: 60%
 AS severity on echo:
0.7 cm2
 BSA: 1.7 m2, indexed AVA: 0.4 cm2/m2
 Peak/mean gradient: 51/29 mmHg
 AVA:
Case Study#2: Discrepancy between AVA
and Gradient
LVEF: 60%
Small LV cavity: LVEDD: 39 mm
LVEDV: 79 ml
GLS: 11%
Dobutamine Stress
Echocardiography
Multislice CT
15 µg/kg/min
Peak ΔP: 94 mmHg
Mean ΔP: 57 mmHg
AVA: 0.77 cm2
Valve Calcium score: 1900 AU
Hachicha Z et al., Circulation.
115:2856-2864, 2007
Potential Causes of Discordance between
AVA (e.g. 0.8) and gradient (e.g. 30) in Pts.
With Preserved LVEF

Paradoxical low-flow, low-gradient severe AS

Measurement errors

Small body size

Inconsistency in guidelines criteria
Dumesnil & Pibarot Circulation 2011; 124:e360
Minners et al. Eur Heart J, 2008
DISCORDANT FINDINGS
AVA<1.0 cm2 &
ΔPmean<40 mmHg
LVEF>50%
STEP #1
Is it real?
Rule out measurement errors:
corroborating methods:
(2D or 3D volumetric meas. SV,
AVA Planimetry by TEE)
Rule out small body size:
Indexed AVA >0.6 cm2/m2
YES
STEP #2
Symptoms?
NO
YES
Close Follow-up
+- Exercise Testing
STEP #3
Is it severe AS?
STEP #3
Is it severe AS?
Features of paradoxical low-flow:
SVi≤35 mL/m2 Zva>4.5
EDD<47 mm EDVi<55 ml/m2
RWTR>0.50
GLS<15%
PRESENT
Consider paradoxical low-flow, low-gradient AS
Rule out pseudo-severe AS:
Dobutamine/exercise stress echo
Calcium score by CT
BNP
ABSENT
Consider inconsistencies in guidelines criteria
Moderate/Severe AS
Close Follow-up
YES
Consider paradoxical low flow SEVERE AS
Consider AVR/TAVI