©2013 MFMER | 3289956-1
Assessment and Management of Low Flow Low Gradient AS with Preserved LV Systolic Function
Joseph F. Malouf MD, FACC, FAHA, FASE Director, Interventional Echocardiography
Professor of Medicine Mayo Clinic
No Disclosures
©2013 MFMER | 3289956-2
Objectives
• Describe potential reasons for discordant AS severity criteria
• Understand the pathophysiology of low flow low gradient (LG) “Severe” AS with preserved EF
• Review prevalence and clinical significance of LF LG “Severe” AS with preserved EF
©2013 MFMER | 3289956-3
1. Measurement errors
2. Small body size
3. Paradoxical LF severe AS
4. Intrinsic discrepancies in guidelines criteria
5. Any of the above
CP1283942-3
Question 1
In Aortic Stenosis with EF > 50%, possible reasons
for an AVA < 1 cm2 and mean gradient < 40 mm Hg
include:
©2013 MFMER | 3289956-4
Question #2 Which of following statements is NOT correct regarding paradoxical low flow low gradient
severe aortic stenosis?
1. Most studies show better outcomes compared to patients with high-gradient severe AS
2. There is a higher prevalence of heart failure (HFpEF)
3. Most studies show benefit from aortic valve replacement
4. Arterial and global afterload are increased
©2013 MFMER | 3289956-5
Question #3 What is your initial recommendation for treating
a 73 year old man with hypertension (160/94 mmHg), dyspnea, paradoxical LFLG severe AS,
and STS score of 6?
1. Vasodilator therapy
2. Surgical aortic valve replacement
3. TAVR
4. Decide after Dobutamine Stress Test
©2012
MFMER |
3200268v2(
2003)-5
88 yo female with progressive
DOE and no lung disease
or known CAD
EF 59%
LVMI 95 g/m2
RWT=0.57*
RVSP 60 mmHg
TR vel 3.4 m/s
Mild MR
MildTR
RWT= 2x PWed
LVEDD * ≥0.42
©2013 MFMER | 3289956-8
What would you recommend?
1. Aortic valve replacement
2. Discordant mean gradient and valve
area – repeat TTE
3. Dobutamine stress echo
4. Hemodynamic cardiac cath.
5. CT scan of the aortic valve
©2013 MFMER | 3289956-9
Grading Severity of
Aortic Stenosis
Mean gradient AVA
Mild <30 >1.5
Moderate 30-40 1.0-1.5
Severe >40 <1.0
CP1006390-34 AHA/ACC Valve Guidelines 2014
©2013 MFMER | 3289956-10
Discordant “Severe” AS by AVA and
MG in pts with nl LV EF
Mean gradient AVA
Mild-Mod <40
Severe <1.0
CP1006390-34
©2013 MFMER | 3289956-11
Aortic Valve Area by Echo Continuity Equation
©2012 MFMER |
slide-11
=
AVA x
LVOT Area LVOT TVI
AV TVI
STROKE VOLUME
©2013 MFMER | 3289956-12
1. Inaccurate LVOT diameter
2. Underestimated LVOT velocity/TVI
3. Underestimated AV peak velocity
4. SV (small LV , systolic function, SVR )
Measurement Errors
CP1283942-3
Michelena et al Heart 2013
©2013 MFMER | 3289956-14
The critical issue of LVOT diameter measurement
• Underestimation of LVOT diameter is ♯1 error leading to the false conclusion of severe AS
• This also leads to underestimation of stroke volume and to the false conclusion of “Low-Flow”
• LVOT diameter should be re-checked (several times) on closer examination
• TEE may be useful in case of poor image quality
LVEF = 60% (Biplane Simpson)
TVI LVOT= 12 cm
Stroke volume: 42 ml
Svi: 23ml/m² (32-58)
Mean gradient: 24 mmHg
AVA: 0.8 cm2 (0.45
cm²/m²)
Global longitudinal strain is markedly decreased
normal values ≥ -20%
GS -12% GS -10.9%
©2013 MFMER | 3289956-17
Herrmann S et al JACC 58:402, 2011
Low Flow Etiologies
Pibarot and Dumesnil Circulation 2013
Low flow, low gradient in severe aortic stenosis (AS) due to concomitant cardiovascular diseases.
Sorin V Pislaru, and Patricia A Pellikka Heart 2016;102:665-671
©2012 MFMER | 3200268v2(2003)-20
Severe AS with AV velocity < 4 m/sec ?
Velocity = 3.8 m/sec
Mean Gradient = 38 mmHg
From Apex
From Right Parastetnal position
Velocity = 5.6 m/sec
Mean Gradient = 72 mmHg
©2013 MFMER | 3289956-21
Optimal Doppler Velocity Location Depends on Aortic Root Angulation
• Overall, the highest AV velocity comes from RPS in 50%
• If the angle<115 degree, it is from RPS in 67%
• AS/MG is underestimated in 15% if only apex is used
©2011
MFMER |
slide-21 J. Thaden and J. Oh et al. ACC 2014
©2013 MFMER | 3289956-22
What is the Prevalence of Discordant Aortic
Stenosis Echo-Doppler derived measurements?
3,483 Echocardiographic Studies in
Patients with Aortic Valve Stenosis and
Normal Left Ventricular Function
Minners et al: EHJ 29:1043, 2008
2.0
1.5
1.0
0.5
0 20 40 60 80 100 120
39% 30%
Valv
e a
rea (
cm
2)
Mean pressure gradient (mm Hg)
1% 30%
Stroke Volume from 3,349 Echocardiographic
Studies in Patients with Aortic Valve Stenosis
Nl LV function; AVA 2
Consistent grading
AVA (cm2) 1
Pm (mm Hg) 40
n 983
Stroke volume (mL) 79±15*
Minners et al: EHJ 29:1043, 2008
Inconsistent grading
AVA (cm2) 1
Pm (mm Hg) >40
n 20
Stroke volume (mL) 107±15*
Inconsistent grading
AVA (cm2) <1
Pm (mm Hg) 40
n 997
Stroke volume (mL) 66±11*
Consistent grading
AVA (cm2) <1
Pm (mm Hg) >40
n 1,338
Stroke volume (mL) 70±14*
Stroke Volume from 3,349 Echocardiographic
Studies in Patients with Aortic Valve Stenosis
Nl LV function; AVA 2
Minners et al: EHJ 29:1043, 2008
Inconsistent grading
AVA (cm2) <1
Pm (mm Hg) 40
n 997
Stroke volume (mL) 66±11*
Consistent grading
AVA (cm2) <1
Pm (mm Hg) >40
n 1,338
Stroke volume (mL) 70±14*
Stroke Volume from 3,349 Echocardiographic
Studies in Patients with Aortic Valve Stenosis
Nl LV function; AVA 2
Minners et al: EHJ 29:1043, 2008
Inconsistent grading
AVA (cm2) <1
Pm (mm Hg) 40
n 997
Stroke volume (mL) 66±11*
Consistent grading
AVA (cm2) <1
Pm (mm Hg) >40
n 1,338
Stroke volume (mL) 70±14*
©2013 MFMER | 3289956-27
What is the clinical significance of truly
discordant AS severity data?
©2013 MFMER | 3289956-28
Causes of True Discordance in Pts with Low Flow Low Gradient Severe AS
Paradoxical low flow, low gradient, severe AS
Inconsistency in guidelines criteria for severe AS
SV: 51 ml
AVA: 0.7 cm2
∆P: 25 mmHg
Normal Flow sAS
LVEF: 60%
SV: 69 ml
AVA: 0.7 cm2
∆P: 45 mmHg
LVEDV: 115 ml
Paradoxical Low Flow
sAS
LVEDV: 85 ml
Pibarot & Dumesnil JACCI 2009 Pibarot & Dumesnil JACC 2012
LVEF: 60%
Lancelloti et al JACC 2012;59:235
Clinical Outcome in Severe Asymptomatic AS (AVA <1cm2); LV EF ≥55%
LF=SV< 35 cc/m2
Aortic Valve Area vs Mean Gradient Based on Gorlin Equation
Carabello B. Aortic Stenosis NEJM 2002
©2013 MFMER | 3289956-33
50 53
352
1249
Flow Gradient Patterns in Severe AS (AVA<1 cm2) with Preserved EF
(n = 1704)
LF/HG (SVI<35, MG≥40)
LF/LG (SVI<35,MG<40)
NF/LG (SVI≥35, MG<40)
NF/HG (SVI≥35, MG≥40)
3%
21%
73%
3%
©2013 MFMER | 3289956-34
Survival to Death Under Medical Management
0
20
40
60
80
100
0 1 2 3
Su
rviv
al (%
)
At risk, no. (%)
NF/LG 190 (91.0) 112 (82.3) 65 (72.7)
NF/HG 223 (83.0) 108 (66.9) 56 (52.7)
LF/LG 23 (82.5) 8 (44.1) 3 (27.6)
LF/HG 8 (80.8) 5 (80.8) 1 (60.6)
NF/LG
NF/HG
LF/LG
LF/HG
Years
Eleid MF et al. Circulation 2013;128:1781-9.
P<0.0001
©2013 MFMER | 3289956-35
LF/LG Patient Characteristics
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
Atrialfibrillation
Previousheartfailure
Obesity Anysymptoms
LF/LG
NF/LG
NF/HG
P < 0.0001 for all
Eleid MF et al. Circulation 2013;128:1781-9.
SVI is incrementally associated with Mortality
Eleid MF et al. Heart 2015;101:23-9.
©2013 MFMER | 3289956-38
0
20
40
60
80
100
0 1 2 3 4 5
Overall Survival in Patients with NF vs PLF Asymptomatic Severe AS
as a Function of the Type of Treatment Medical vs Surgical
Surv
ival (%
)
Follow-up (years)
P<0.001 (0.002; 0.017)
PLF surgical
NF surgical
NF medical
PLF medical
Hachicha Z et al Circulation 2007; 115:2856
Copyright © American Heart Association, Inc. All rights reserved. Dania Mohty et al. Circulation. 2013;128:S235-S242
AVR+/- CABG
Isolated AVR
Surgery or Conservative Management
Copyright © American Heart Association, Inc. All rights reserved. Dania Mohty et al. Circulation. 2013;128:S235-S242
AVR+/- CABG
Isolated AVR
Surgery or Conservative Management
Operative mortality
LFLGsAS=9.8%
NFHGsAS=3.8%
Mean FU 4.6 yrs
Copyright © American Heart Association, Inc. All rights reserved. Dania Mohty et al. Circulation. 2013;128:S235-S242
AVR vs Conservative Management in pts with LF-LG AVA≤ 1cm2 & EF>50%
LF=SV< 35 cc/m2
Le Ven et al JACC 2013
TAVR
67 year old woman with severe aortic stenosis
and heart failure came to Valve Clinic for AVR
Stroke volume = (1.9) 2 x 0.785 x 21 = 60 cc (SVI =30)
AVA = 60 / 76 = 0.79 cm2
MG 26 mmHg
LVOT D = 1.9 cm LVOT TVI = 21cm
Restrictive Diastolic Filling
Mitral inflow
Mitral Annulus
E/e’ =25
E’ = 4cm/sec
©2013 MFMER | 3289956-45
Two Obstructions in Series
Gross specimen photo courtesy of Dr. William Edwards
Hachicha et al. Circulation. 2007;115:2856-64
AKA Valvulo-Arterial Impedance
Characterization of 512 Consecutive Patients with Severe AS
(IAVA<0.6 cm2/m2)&EF>50%
Group 1
“Normal flow, high gradient”
SVi >35 mL/m2
Gradient >40 mmHg
n=152 (30%)
Indexed AVA=0.4±0.1 cm2/m2
LVEDD=48±5 mm
LVEDVI=59±13 mL/m2
ZVA=4.2±0.8 mmHg/mL/m2
AVR=80%
Group 2
“Normal flow, low gradient”
SVi >35 mL/m2
Gradient 40 mmHg
n=193 (38%)
Indexed AVA=0.5±0.1 cm2/m2
LVEDD=48±5 mm
LVEDVI=58±13 mL/m2
ZVA=4.0±0.6 mmHg/mL/m2
AVR=53%
Group 3
“Low flow, high gradient”
SVi 35 mL/m2
Gradient >40 mmHg
n=44 (8%)
Indexed AVA=0.3±0.1 cm2/m2
LVEDD=43±5 mm
LVEDVI=48±12 mL/m2
ZVA=6.0±1.2 mmHg/mL/m2
AVR=68%
Group 4
“Low flow, low gradient”
SVi 35 mL/m2
Gradient 40 mmHg
n=123 (24%)
Indexed AVA=0.5±0.1 cm2/m2
LVEDD=46±5 mm
LVEDVI=53±11 mL/m2
ZVA=5.2±1.3 mmHg/mL/m2
AVR=36%
Dumesnil et al: EHJ 31;281, 2010
Co
nc
ord
an
t g
rad
ing
D
isco
rda
nt g
rad
ing
Eleid MF et al. Circulation 2013
Eleid MF et al. Circulation 2013
©2013 MFMER | 3289956-50
How Much of the Problem is the Valve?
Medical therapy
Surgery
Ventricular-Vascular Coupling
Ventricular-Vascular Coupling
Mackram F. Eleid et al. Circulation. 2013;128:1349-1353 Copyright © American Heart Association, Inc. All rights reserved.
Ventricular-Vascular Coupling
Jordi S Dahl et al. Heart 2015;101:1015-1023
RWT= 2x PWed
LVEDD
Serial changes LFLGsAS vs NFHGsAS vs NFLGsAS
LFLGsAS=78 pts; NFHGsAS=156pts
Jordi S Dahl et al. Heart 2015;101:1015-1023
Copyright © BMJ Publishing Group Ltd & British Cardiovascular Society. All rights reserved.
Serial changes LFLGsAS vs NFHGsAS vs NFLGsAS
LFLGsAS=78 pts; NFHGsAS=156pts
Development of severe aortic stenosis (AS).
Sorin V Pislaru, and Patricia A Pellikka Heart 2016;102:665-671
Proposed systematic approach to diagnosis of low-flow/low-gradient severe aortic stenosis.
Sorin V Pislaru, and Patricia A Pellikka Heart 2016;102:665-671
CP1303877-3
Schroeder et al EHJ 29: 531 2008
Indications for Aortic Valve Replacement in Patients With Aortic Stenosis