Variants of AS Including Low Flow

Variants of AS: Low Flow
Howard C. Herrmann, MD
University of Pennsylvania
All Aortic Stenoses Are Not Created Equal
Anjan and Herrmann, JACC 2015;65:654-6
Sensitivity and Specificity of Different Techniques for Detecting
Critical AS (AVA <0.8 cm2) Results in Many Misclassifications
100%
100%
97%
97%
93%
97%
92%
84%
81%
80%
78%
72%
60%
Sensitivity
57%
53%
Specificity
42%
40%
36%
20%
0%
Cath-BSA
Cath-Weight
Cath-LaFarge
Cath-TD
Referenced to Cath-mVO2
Echo-2D
Cath-mVO2
Cath-TD
Referenced to Echo-3D
• 16% w/o critical AS on 3D were critical with 2D echo
• 43% w/o critical AS on TD were critical with mVO2
Gertz and Herrmann,
Circ CI 2012;5:406-414,
Errors and Flow Dependence of Calculated AVA
Hemo assessment with Gorlin (1951)
calculation of orifice area assumes:
Constant coefficient of orifice contraction
at varying transvalvular flow rates
Constant coefficient of velocity (energy
dissipation due to friction and turbulence)
Dependence on accuracy of CO method
Echo uses direct measure of Doppler velocity
and continuity equation (Koutsurakis, Warth
1984), but assumes:
Laminer flow
Flat velocity profiles both pre valve and at
the orifice
Parallel Doppler signal
Circular LVOT and accurate measure of
LVOT
Canine model of chronic AS (22% increase in
AVA with 100% increase in flow)
Burwash et al, Circ 1994;89:827-835
SVI Only Multivariable Predictor of Difference
Between Invasive and Non-Invasive Assessment
1.00
Low Flow = LVSVI < 35 mL/M2
0.80
Echo 3D - Cath-mVO2 AVA
0.60
y = -0.016x + 0.539
r = -0.591; p=0.001
0.40
0.20
0.00
0
10
20
30
40
50
60
70
80
90
100
-0.20
-0.40
-0.60
-0.80
-1.00
Stroke Volume Index (mL/m2)
 Echo AVA is higher at low flow
 Cath AVA higher at higher flow
Gertz and Herrmann, Circ Intv 2012
Treatment of LF AS:
What do the Guidelines Say?
ACC/AHA
2008
ESC/EACTS
2012
Classic LF AS with CR
Classic LF AS w/o CR
Paradoxical LF
No
Specific
Recs
ACC/AHA
2014
II a, C
II a, B
II b, C
II a, B
II a, C*
II a, C#
* “only after careful confirmation of severe AS”
#
“if clinical, hemodynamic, or anatomic data support valve obstruction as
the most likely cause for symptoms”
ACC/AHA 2008 (Bonow et al, Circ and JACC)
ESC/EACTS 2012 (Vahanian et al, EHJ)
ACC/AHA 2014 (Nishimura et al, Circ and JACC)
Pibarot and Dumesnil, JACC 2012
Resting AVA at Normal Flow Reflects True AVA
 Flow rate =
SV
SEP
•
Incorporates both EF and SVI
•
Normal is > 200 ml/s
 In pts with suspected LF LG AS, if
resting flow is normal, AVA is
unlikely to change with stress
echo evaluation
 Resting flow was the only
independent predictor of true
severe AS (not EF or SVI) with a
pos pred value of 84%
Chahal et al, JACC CV Imag 4.21.2015 online
MDCT Aortic Valve Calcification
Predicts Severity and Survival in AS
Cueff C et al. Heart 2011;97:721-726
Clavel et al, J Am Coll Cardiol.
2014;64(12):1202-1213
Studies of Outcomes of Surgery in
Classical LF LG severe AS
Series
LF, LG, LEF
Blitz, 1998
Monin, 2003
Kulik, 2006
Clavel, 2008
Levy, 2008
N
Peri-op or 30 day Mortality*
52
95
79
44
217
11%
14%
8%
18%
16%
1-year (Mortality) 5-year
LF, LG, LEF
Blitz, 1998
Monin, 2003
Kulik, 2006
Clavel, 2008
Levy, 2008
52
95
41 (no AVR)
79
44
57 (no AVR)
217
29%
25%
60%
11%
30%
30%
25%
*Percentages approximated by extrapolation from KM curves; #~50% AVR
34%
24%
51%
Surgery Improves Outcome Independent of Flow Reserve
Monin et al, Circulation 2003;108:319
Outcome and Impact of Surgery in Paradoxical Low-Flow,
Low-Gradient Severe Aortic Stenosis and Preserved Left
Ventricular Ejection Fraction in 768 patients
Conclusion:
LF LG NEF AS has worse prognosis (HR 1.85), higher
peri-op mortality (9.8% vs 4%), but better long-term
outcome with surgery
Mohty et al, Circulation 2013;128:S235
Dimensionless Index (DI) Predicts Event-Free
Survival in Paradoxical LF AS
• DI calculated as the ratio
of LV and Aortic VTI
• 488 patients with mod or
severe AS and preserved
LV EF
Rusinaru and Tribouilloy, JACC Cardiol Img 2015;8:766-75
Studies of Outcomes of Surgery in
LF LG NEF severe AS
Series
N
1-year
(Mortality)
5-year*
Hachicha,2007
80 (AVR)
91 (Std Rx)
5%
20%
15%
60%
Tarantini, 2011
73 (AVR)
29 (Std Rx)
10%
25%
20%
80%
Jander, 2011
435 (Std Rx)
2%
10%#
Clavel, 2012
150 (AVR)
10%
18%
37 (Std Rx)
18%
55%
83 (AVR)
18%
37%
16 (Std Rx)
32%
62%
Mohty, 2013
*Percentages approximated by extrapolation from KM curves; #~50% AVR
How does TAVR differ from Surgery?
• TAVR is less invasive:
–
–
–
–
Faster recovery
Less pericardial irritation with potential for less AF
Less healing, risk for infection
Shorter ventilator dependency
• Cardiopulmonary bypass can be detrimental:
– Systemic inflammatory response syndrome
· Inflammatory activation by membrane oxygenator, heparin-coated circuits, UF
· Ischemia-reperfusion injury to various organs (gut, kidneys, brain, etc)
– Risk for adverse cerebral effects (cognitive decline)
– Need for higher levels of anticoagulation
– Need for cardiac standstill with cardioplegia and hypothermia
• Larger effective orifice area (EOA) with transcatheter vs
surgical prostheses:
– Less Patient-Prosthesis Mismatch (PPM)
– PPM may be more important in low flow, low EF with heightened
afterload sensitivity
Results
KM mortality for LF vs NF
ITT - Cohorts A & B
70%
HR: 1.52 [95% CI: 1.24, 1.87]
Log-Rank p= <.001
LF (Low Flow)
NF (Normal Flow)
2-Yr Death (%)
60%
2-Yr Death (%)
ITT - Cohorts A & B
80%
70%
60%
50%
40%
30%
20%
10%
0%
48.9%
46.1%
0
50%
HR: 1.07 [95% CI: 0.83, 1.37]
Log-Rank p= 0.616
LF LEF
LF NEF
4
8
47.2%
30%
33.9%
LF LEF LG
NF LEF NG
225
304
20%
177
214
154
213
142
193
20
24
128
179
119
162
100
134
ITT - Cohorts A & B
0%
0
4
8
16
20
24
Months
Numbers at Risk
530
441
12
422
368
368
342
336
317
308
300
282
274
235
239
2-Yr Death (%)
10%
LF
NF
16
Months
Numbers at Risk
40%
12
70%
HR: 0.97 [95% CI: 0.65, 1.44]
Log-Rank p= 0.886
LF LEF LG
LF LEF NG
60%
50.9%
50%
40%
48.0%
30%
20%
10%
0%
0
4
LF LEF LG
NF LEF NG
147
78
12
16
20
24
83
45
76
43
67
33
Months
Numbers at Risk
Herrmann et al, Circulation 2013;127:2316
8
115
62
100
54
94
48
Results
Outcomes in LF vs NF by Treatment Received
(Cohort A)
40%
35%
2-Year Death (%)
log rank p= 0.030
LF – A - TAVR
LF – A - Surgery
NF – A - TAVR
NF – A - Surgery
45%
39.3%
38.1%
28.9%
30%
25.4%
25%
20%
15%
10%
5%
0%
0
60
120
180
240
300
420
480
540
600
660
720
Days
Numbers at Risk
LF – A – TAVR
LF – A – Surgery
NF – A – TAVR
NF – A – Surgery
360
170
180
152
145
152
138
143
127
139
119
135
110
127
123
124
106
123
119
120
102
116
115
117
97
109
111
110
95
102
105
107
89
86
90
95
77
Herrmann et al, Circulation 2013;127:2316
Predictors of Mortality After TAVR
in LF AS
• 984 patients with LF AS (43% PLF) who underwent TAVR
• Stratified into tertiles based on discharge LV SVI
• Increased mort in persistent LF tertile (both classical and PLF)
Predictors of Mortality After TAVR
in LF AS
• SVI improved in all patients
• Independent predictors of mort:
– STS score, gender, AF, persistent mod/severe MR
Conclusions
•
We now recognize a number of AS variants based on complex interactions
between flow, gradient, and ejection fraction
•
Diagnosis of these patients, particularly in the setting of low gradient, is
challenging and requires integration of the echo findings, hemodynamics,
and adjunctive imaging (CT) and testing (DSE)
Untreated low flow severe AS is associated with as much as a 50% higher
mortality regardless of etiology. In this regard, SVI should be incorporated
into the assessment of patients with AS.
AVR in patients with LF severe AS with or without LV dysfunction is associated
with higher peri-operative mortality
Nonetheless, both TAVR and SAVR improve the mid-term survival relative to
medical management. There may be some advantages for TAVR in this
population based on lower procedural risk
Flow will increase after AVR, but identification of remedial causes of
persistent low flow may represent an opportunity to improve outcomes in LF
patients
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