eae-clinical significance of valvulo-arterial …...impact of hypertension on the timing of symptom...

Clinical Significance of Valvulo-Arterial

Impedance in Aortic Valve Stenosis

Dr. Julien Magne, PhD

Sart Tilman Liège, BELGIUM

Conflict of Interest Disclosure

None

Valvulo-Arterial Impedance (Zva): Definition

Mechanical Impedance: a measure of how much a structure resists

motion when subjected to a given force.

In Aortic stenosis: Zva represents the cost in mmHg for each

systemic mL of blood indexed for body size pumped by the left

ventricle during systole.

Zva provides an estimate of the global LV hemodynamic load that

results from the summation of the valvular and vascular loads:

• stenosis severity

• volume flow rate

• body size

• systemic vascular resistance

Static Pressure LVSP

SAP

∆P

MG

AA

Flow axis

Valvular Load

Arterial Load

EOA SV

} }

Valvulo-Arterial Impedance

Zva = = LVSP MG + SAP

SVi SVi

Left Ventricular Afterload in Aortic Stenosis = Valvular Load + Arterial Load

Courtesy from Dr Philippe Pibarot, Quebec Heart and Lung Institute, Qc, Canada.

} Total Load

>3.5: Moderate

>4.5: Severe

Impact of Hypertension on AS Severity

Little et al. Heart, 93:848-55. 2007 Mascherbauer et al.; Eur Heart J; 2008

Impact of Hypertension on the Timing of Symptom Onset in AS

193 patients with symptomatic AS

32% had concomitant HTN

Symptoms of AS develop

at lower degree of stenosis severity

in hypertensive patients, probably

because of the additional overload

due to hypertension.

0,6

0,65

0,7

0,75

0,8

0,85

0,9

AVA (cm2) at symptom onset

Antonini-Canterin et al.; Hypertension. 2003;41:1268-1272.

p=0.02

No

HTN

HTN

Zva

(m

mH

g.m

L-1

.m-2

)

2

3

4

5

6

7

Group 0 Group A Group ABGroup B

*†‡

**

Groups I II III IV (n=208) Moderate AS

Normal SAC

Moderate AS

Low SAC

Severe AS

Normal SAC

Severe AS

Low SAC

(n=77, 37%) (n=50, 24%) (n=45, 22%) (n=36, 17%)

Valvulo-Arterial Impedance (Global LV Afterload)

SAC= PP

SVi

Low SAC: 0.6

ZVA= SAP+MG

SVi

Briand, JACC, 46:291-296,2005

AS and Reduced Systemic Arterial Compliance: Impact on LV Afterload

Moderate AS Severe AS

AS and Reduced Systemic Arterial Compliance:

Impact on LV Function

Norm

SAC

Low

SAC

Norm

SAC

Low

SAC

Briand, JACC, 46:291-296,2005

LV Diast. dysfunction

Zva≥4.5

OR=5.4, p<0.0001

LV Syst. dysfunction

Zva≥4.5

OR=4.2, p=0.001

Features of Patients with Elevated Zva

Hachicha et al., JACC, 2009

Asymptomatic patients

with ≥moderate AS (peak

Ao jet velocity ≥2.5m.s-1)

and LVEF>50%: n=544

Low: Zva≤3.5 mmHg.mL-1.m²

n=172, 32%

Medium: 3.5-4.5 mmHg.mL-1.m²

n=192, 35%

High: ≥4.5 mmHg.mL-1.m²

n=180, 33%

Retrospective analysis of 544 asymptomatic pts

≥ moderate AS (≥ 2.5 m/s), LVEF ≥ 50%; Follow-up 2.5±1.8 years

Prognostic Impact of Global Afterload

Follow-up (years)

Over

all

Su

rviv

al,

(%

)

Multivariate Analysis

Med Zva: HR=2.3; p=0.03

High Zva: HR=2.8; p=0.01

100

80

60

40

20

0

0 2 4 6 8

Zva<3.5

P < 0.001

3 years

88 ± 3%

80 ± 3%

70 ± 5%

3.5≤ Zva<4.5

Zva≥ 4.5

Age-Gender matched

general population


Zva in the SEAS trial

n=1 591 asymptomatic patients

with AS (67±10 yrs, 51% of

hypertensive, 39% of women

In patients with asymptomatic AS without diabetes or known CAD:

• LVEF generally preserved

• LV myocardial dysfunction: 33%

LV myocardial dysfunction:

• common in patients with increased Zva

• especially in the subgroup with low-flow AS

• more concentric LV geometry, LV hypertrophy, and male

Cramariuc et al. JACC CV Img, 2009

Peak aortic velocity ≥ 4.4 m.s-1

Zva ≥ 4.9 mmHg.ml-1.m-2

Longitudinal strain ≤ 15.9 %

Ind. LA area ≥ 12.2 cm2/m2

HR= 1.7, p=0.027

HR= 1.9, p=0.013

HR= 2.2, p=0.003

HR= 2.8, p=0.001

0 1 2 3 4 5

Hazard-ratio

6

Zva in Asymptomatic AS Prospective study: 163 patients with asymptomatic AS and

preserved LV function

Adjustment for gender, systemic arterial compliance, E-wave, E/A

ratio and response to exercise (abnormal vs. normal)

Lancellotti, Donal, Magne et al. Heart, 2010

Zva in LF/LG AS n=184 patients with severe LF/LG AS

included in the French study.

Lévy, Monin et al. EJ Echo, 2011

LVEF

SV

ex. SV

LV contractile

reserve

(ΔSV>+20%)

Zva is inaccurate to

differentiate TS and PS AS

Zva in LF/LG AS

Rest

Qmean= 162ml/s

SVi= 30ml/m²

Rest

MPG= 31mmHg

Zva= 5mmHg/ml/m²

Dobutamine

Qmean= 252ml/s

SVi= 42ml/m²

Dobutamine

MPG= 41mmHg

Zva= 3.8mmHg/ml/m²

20 30 40 50 60 70 80 90 100 110 120 130

1

2

3

4

5

6

7

8

9

Zva

, m

mH

g/m

l/m

² LV stroke volume, ml

Pseudo-severe AS

True-severe AS

Low flow Normal-high flow

BSA was assumed at 1.8 m², LVED

vol at 120 mL, HR at 65 b.p.m., and

SAP at 120 mmHg.

Zva vs. SV in patients with true-severe

and pseudo-severe AS.

Lancellotti and Magne, Editorial, EJ Echo, 2011

Myocardial Function and Zva in Severe AS

Depressed LV longitudinal function,

basal septal and lateral LGE,

elevated myocardial fibrosis score,

and high myocyte diameter

Hermann et al, JACC, 2011

Maximal Exercise Capacity and Zva

0

5

10

15

20

25

3021.5±4.8 21.2±5.1 20.6±5.3 20.3±5.3 20.2±5.3

18.8±5.8 17.6±5.7 15.6±5.3

14.0±5.9 12.3±6.0

p=0.079 p=0.014 p=0.007 p=0.008 p=0.006

VO

2 m

ax,

mL

/kg/m

in

Valvulo-Arterial Impedance (Zva), mmHg/mL/m²

Dulgheru et al. ESC meeting 2012

Blood pressure should be routinely measured in the echo lab.

and Zva calculated

High Zva in AS patients is an accurate marker of advanced

stage of the disease and is associated with reduced maximal

exercise capacity

High Zva is associated with poor mid- and long-term outcome,

even in asymptomatic patients

In patients with severe asymptomatic AS and high Zva, follow-

up could be shorten and exercise test and/or exercise echo should

be recommended

Conclusion

DON’T MISS

5-8 December 2012

MAICC – Athens, Greece

Abstract submission deadline

31 May

Early bird registration

30 September

Thank you for your

attention.

“In these matters the only certainty is

that nothing is certain.”

Pliny The Elder, 23 AD-79 AD

“Severe” AS with Low Gradient and

Low LVEF

AVA 1.0 cm2

Mean gradient 30-40 mmHg

LVEF 40%

Approximately 5-10% of AS population

High risk patients:

3-year survival 50-60%

If operated (AVR): operative mortality: 8-30%

Sténose Aortique

Prospective Studies: Topas/Euro Trial Severe AS, LG, Low LVEF

Follow-up, (month)

Su

rviv

al,

(%

)

0 12 24

0

20

40

60

80

100

36

70%

at 1 yr 61% at

2-yr

57% at

3-yr

Operative mortality: 18%

Follow-up, (month)

Su

rviv

al,

(%

)

0

20

40

60

80

100

0 12 24 36 48 60

Operative mortality: 16%

49% at

5-yr

Topas Study European Multicenter Study

Levy et al. JACC, 51:1466-72, 2008

n=101 n=217

Clavel et al. Circulation, 2008

Usefulness of Dobutamine Stress Echo (DSE) in LF/LG AS

Echo Rest

10.0 5.0

20.0 15.0

8 min 8 min 8 min 8 min

Monitoring: ECG, blood pressure

Infusion protocol

Low Flow, Low Gradient Severe AS

AVA <1.0 cm2, DPmean <30-40 mmHg, LV EF ≤40%

Dobutamine Stress Echocardiography

Stenosis Severity

(True vs. Pseudo Severe AS) Contractile Reserve

Low Flow Low Flow High Flow High Flow

True Severe AS Pseudo Severe AS

True Severe AS vs. Pseudo Severe AS ?

∆P

AVA

Risk Stratification in LF/LG Severe AS, Low LVEF

Levy et al. JACC, 51:1466-72, 2008

Clavel et al. Circulation, 2008

Risk Stratification in LF/LG Severe AS, Low LVEF

Dobutamine Sress Echo

SV ≥ 20 %

Contractile Reserve No Contractile Reserve

SV < 20 %

AVR? MEDICAL?

AVR CABG

ΔP>30-40 AVA≤1.0

Pseudo Severe AS

MEDICAL

ΔP≤30-40 AVA>1.0

True Severe AS Indeterminate

ΔP<30-40 AVA≤1.0

ΔP<30-40 AVA≤1.0

Follow-up, (month)

Su

rviv

al,

(%

)

0

20

40

60

80

100

0 12 24 36 48 60

Su

rviv

al,

(%

) 0

20

40

60

80

100

Follow-up, (month)

0 12 24 36 48 60

AVR AVR

Medical Medical

54±7%

13±7%

65±11%

11±7%

p=0.0001 p=0.019

Whole Cohort (n=81) Matched Cohort (n=42)

Ouctome after AVR in Patients without

Contractile Reserve

Tribouilloy et al. JACC, 2009 Operative Mortality: 22%

Ouctome after TAVI in LF/LG

Severe AS

Partner Study

TAVI

Better

AVR

Better

LVEF≤55%

LVEF>55%

Smith et al., NEJM, 2011

TAVI in LF/LG

Early mortality: 33%, p=0.037

Gotzmann et al., Cath CV Interv, 2011

SEVERE AS PRESERVED LV FUNCTION

(AVAi ≤ 0.6 cm²/m²) (LVEF ≥ 50%)

331 patients (65%)

SVI > 35ml/m²

Normal Flow (NF) Group

181 patients (35%)

SVI ≤ 35ml/m²

Paradoxical Low Flow

(PLF) Group

n=512

SV: 50 ml

AVA: 0.7 cm2

∆P: 25 mmHg

Normal Flow AS

LVEF: 60%

SV: 70 ml

AVA: 0.7 cm2

∆P: 45 mmHg

LVEDV: 115 ml

LVEF: 60%

Paradoxical Low Flow

AS

LVEDV: 85 ml

Pibarot & Dumesnil iJACC; 2:400-3, 2009

Outcome of Patients with Paradoxical Low Flow

Hachicha Z et al., Circulation.

115:2856-2864, 2007

Over

all

Su

rviv

al

(%)

NF: Normal Flow: SVI>35 (65%)

PLF: Paradoxical Low Flow: SVI≤35 (35%)

Follow-up (years) 0 1 2 3 4 5

0

20

40

60

80

100

p< 0.001

Surgical

Surgical

Medical

Medical

Hachicha

2006

Echo

(512 pts)

Barasch

2006

Echo

(215 pts)

Lancellotti

2010

Echo

(173 pts)

Cramariuc

2009

Echo

(1591 pts)

Minners

2010

Echo

(333 pts)

Minners

2010

Cath

(333 pts)

Jander

2011

Echo

(1525 pts)

Adda

2012

Echo

(340 pts)

Lancellotti

2012

Echo

(150 pts)

Asympt.

Prevalence of PLF/LG Severe AS

≈ 5-15% of Severe AS

Pre

vale

nce

, %

Echo Features of Paradoxical

LF/LG Severe AS

The Aortic Valve:

AVA< 1.0 cm2 AVAi < 0.6 cm2/m2

Severely thickened/calcified valve

Mean gradient <40 mmHg

Valvulo-arterial impedance > 4.5 mmHg.ml-1.m-2

The Left Ventricle

EDD<47 mm EDV< 55 mL/m2

RWT ratio > 0.50

Impaired LV filling

LVEF > 50%

GLS < 16% GRS < 30%

SVi < 35 mL/m2

Advanced Echo Features of

Paradoxical LF/LG Severe AS

-30

-25

-20

-15

-10

-5

0

LV

Str

ain

, %

0

10

20

30

40

50

60

70

NF/HG

NF/LG LF/HG

LF/LG

Radial

GLS LS base

LS mid

LS apex Circ

Adda et al, Circulation CV Img, 2012

LV

Str

ain

, %

Myocardial Function in Paradoxical LF/LG Severe AS

Characterized by similar

LVEF and AVA but lower

MPG and LV SV

Weidemann, Hermann et al, Circ, 2009

Depressed LV longitudinal

function, basal septal and

lateral LGE, elevated

myocardial fibrosis score, and

high myocyte diameter

Hermann et al, JACC, 2011

Absent:

Consider inconsistencies in

guidelines criteria

Rule out measurement errors:

corroborating methods:

(Teichholz, Simpson, 3D-contrast,

AV Planimetry)

Rule out small body size:

AVAi>0.6 cm2/m2

Discordant Findings:

AVA<1.0 cm2 &

ΔPmean<40 mmHg

LVEF>50%

Consider paradoxical low flow severe AS:

AVR

Rule out pseudo-severe AS:

Valve morphology by echo

Exercise/dobutamine stress echo

Calcium score by CT

BNP

Present:

Consider paradoxical low flow AS

Features of paradoxical low flow:

SVi≤35 mL/m2 Zva>4.5

EDD<47 mm EDVi<55 ml/m2

RWTR>0.50 GLS<16%

Outcome of Paradoxical LF/LG

Severe AS

SEAS trial

n=1 873

LVEF≥55%

n=1 525

LG Severe AS

n= 435, 29%

Severe AS

n= 35, 2%

Mod. AS

n= 184, 12%

Jander et al, Circulation, 2011


Severe AS

Su

rviv

al,

(%

)

0

20

40

60

80

100

Follow-up, (month)

0 12 24 36 48 60

Su

rviv

al,

(%

)

0

20

60

80

100

Follow-up, (month)

0 12 24 36 48 60

p=0.48

40

p=0.64

Aortic Valve Events Major CV Events


Moderate AS

Severe LG AS

Severe AS



SV= LVEFxLVED vol 77.1 82.9

BSA: 1.83m² vs. 1.94m²

SVi: 42.1 vs. 42.7 mL/m²

AVA: 0.99 vs. 1.01 cm²

AVAi: 0.54 vs 0.52 cm²/m²

Similar AS severity,

similar outcome!

Asymptomatic Paradoxical LF/LG

Severe AS

Asymptomatic severe AS with

preserved LV ejection fraction,

n=150

Asymptomatic Paradoxical LF/LG

Severe AS

Follow-up, months

Ad

just

ed i

nci

den

ce o

f ca

rdia

c e

ven

ts, %

p=0.009 LF/LG group

NF/LG group

NF/HG group

LF/HG group

Key Messages The presence of a moderately increased transvalvular

gradient (<40 mmHg) does not exclude the presence of a

severe AS, even in patients with preserved LVEF

DSE is very useful for the management of LF/LG AS

Paradoxical LF/LG entity is found in 5-15% of AS

patients and is often associated with more advanced

stage of the disease and worse prognosis, even in

asymptomatic patients

It is important to recognize this entity so we do not deny

surgery to a symptomatic patient with small AVA and

LG

Thank you for your

attention.




DON’T MISS

5-8 December 2012

MAICC – Athens, Greece

Abstract submission deadline

31 May

Early bird registration

30 September

Thank you for your

attention.




eae-clinical significance of valvulo-arterial …...impact of hypertension on the timing of symptom...

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