1) The management of asymptomatic severe aortic stenosis is complex due to uncertainties in assessing risk. 2) Exercise stress testing and biomarkers like BNP can help identify higher-risk asymptomatic patients who may benefit from earlier surgery. 3) Dobutamine stress echocardiography can help determine if low-flow, low-gradient aortic stenosis is true severe stenosis amenable to surgery or pseudostenosis better managed medically. Integrating all clinical and test results is important for individualizing treatment decisions in these patients.

1. Asymptomatic Severe Aortic
Stenosis – Cardiologist’s
Confusion and Surgeon’s
Dilemma
Dr. Imran Ahmed
DM. (Cardiology)

2. Foreword
"We, like most
cardiologists, no longer
believe that surgery is
the most common cause
of sudden death in
asymptomatic patients
with aortic
stenosis“….[McCann GP.
BMJ. 2004;328]
“Transcatheter aortic
valve implantation will
soon become the
procedure of choice for
patients at high risk….”
[BABALIAROS V. Cleveland CJM.
July 2012;79(7)]

3. Severe Aortic Stenosis – A public health
problem ??
• AS is the most common valvular disease
• Worldwide 3rd most prevalent form of CVD
• Reported prevalence of 2-7% in >65 yrs
• Nearly 800,000 (>75 yrs) with severe AS
• Adding AS patients from other age ranges
& different etiologies – can be considered
a public health problem!
[Katz M. Severe aortic stenosis in asymptomatic patients: the dilemma of
clinical versus surgical treatment. Arq. Bras. Cardiol. Vol95(4) Oct. 2010]

5. Asymptomatic Severe Aortic Stenosis
• Severe AS who do not present with classic
symptoms – dyspnea, syncope & angina
• Concept of “benignity” contested since -
- “pseudo-asymptomatic” – pts limit their
activities, thus masking symptoms
- Heterogenous set of patients – maybe
asymptomatic / without LV dysfunction,
other variables ↑ or ↓ risk

6. Benefits of Surgery in AS
• Mortality is 75% at 3 years without surgery
• 8% to 34% with symptoms die suddenly
• Advances in aortic valve surgery - death
rate during last decade in isolated AVR ↓
from 3.4% to 2.6%. [STS database 2006]
• Patients who survive surgery enjoy near-
normal life expectancy: 99% survive 5 yrs,
85% 10 yrs, and 82% at least 15 years
• Nearly all have improvement in their EF
and heart failure symptoms

7. Benefits of Surgery in AS
“Survival benefit of AVR was independent
of clinical, pharmacologic, & echo predictors.
The authors recommend that the threshold
for AVR in patients with severe AS should be
lowered to include asymptomatic patients”
[Pai RG et al. Ann Thorac Surg 2006;82:2116-2122]

8. Benefits of Surgery in Asymptomatic Severe AS
[Pellikkaet al Study]
• Study of 622 patients followed for 5 years
• Probability of remaining symptom-free
(without surgery) was 33% in 5 yrs
• Probability of survival without surgery was
25% in 5 yrs
• Risk of sudden death was ~ 1% a year
• At 2 years of follow-up, the asymptomatic
patient showed a worse prognosis than
that of gen popn, even in absence of symp

9. Figure 1. Survival free of symptoms censored at aortic valve surgery.
Pellikka P A et al. Circulation 2005;111:3290-3295
Copyright © American Heart Association

10. Risk of Routine AVR in Asymptomatic Severe AS
• A routine approach would be exposing
100% of asymptomatic patients to a 3% to
4% risk related to the surgical procedure
• Also an added 1% risk a year related to the
presence of valvular prosthesis,
• Benefiting only approximately 1% of this
population who would present the risk of
sudden death per year
[Katz M et.al. Arq. Bras. Cardiol. vol.95 no.4 Oct. 2010]

11. Surgical AVR - Easy Decision-making
Situations
• Severe symptomatic stenosis [Class IB]
• Asymptomatic severe AS with a low
ejection fraction (<50%) [Class IC]
• Asymptomatic severe AS in patients
undergoing other cardiac surgery [Class IB]
• Asymptomatic moderate AS in pts
undergoing other cardiac surgery [Class IIB]

12. Decision-making in Asymptomatic Severe AS
– Reasons for Ambiguity
• ACC definition of severity ??
• Correlation of valve area and gradients ??
• Cases of low gradients but AVA <1cm2 ??
• Conditions of LV dysfunction without low
EF ??
• Asymptomatic AS/pseudo-symptomatic ??

13. AVA of 1.0 cm2 yields a gradient of 26 mmHg
AVA ≤0.81 cm2 necessary to yield gradient ≥40 mmHg
Therefore guidelines per se are inherently inconsistent
[DumesnilJG. EurHeartJ 2010;31:281–289]

14. Proposed New Severe AS grading Classification
Miners and Dumesnil et. al.

15. Normal flow-low gradient AS
• This pattern observed in 31-38% of pts
• Seems to identify a group of patients with
- a less severe degree of AS
- exposed to the disease for a shorter time
• Characterized by
- preserved LV longitudinal myocard func
- lower BNP level and Monin's risk score
• Prognosis seems to be relatively preserved
NF defined as LV stroke volume >35 mL/m2
LG defined as mean trans-aortic pressure gradient <40 mmHg

16. Normal flow - High gradient AS
• Most prevalent pattern (39-72%)
• Fully consistent with ACC severity criteria
• When compared with NF/LG group –
- LV longitudinal function still preserved
- BNP is higher
- cardiac event-free survival rate reduced
• More severe AS suggesting long exposure
• Symptomatic - classically referred for AVR
• Asymptomatic - optimal risk stratification
NF defined as LV stroke volume >35 mL/m2
HG defined as mean trans-aortic pressure gradient > 40 mmHg

17. Low flow - High gradient AS
• This pattern accounts for 8% of patients
• Characterized by an
- SVi<35 mL/m2 inspite of preserved EF
- High BNP level and Monin's risk score
- Significant reduction in LV long function
• Outcome nearly identical to NF/HG
• When symptomatic, these patients tend to
have a better survival if treated surgically
LF defined as LV stroke volume <35 mL/m2
HG defined as mean trans-aortic pressure gradient > 40 mmHg

18. Mechanism of Low flow - High gradient AS
• LV EF is influenced by both intrinsic
myocardial function & LV cavity geometry
• For a similar extent of intrinsic myocardial
shortening, the LV EF will increase in
relation to extent of LV conc remodelling
• The LV EF therefore underestimates the
extent of myocardial impairment in the
presence of LV concentric remodelling

19. Low flow - Low gradient AS
• Accounts for 7-35% (>in symptomatic) AS
• Characterized by
- pronounced LV concentric remodelling
- smaller LV cavity
- increased global LV afterload
- intrinsic myocardial dysfunction/fibrosis
• This clinical entity is often misdiagnosed -
leading to underestimation of AS severity
LF defined as LV stroke volume <35 mL/m2
LG defined as mean trans-aortic pressure gradient < 40 mmHg

20. Low flow - Low gradient AS
• Dismal prognosis - In asymptomatic pts,
likelihood of survival without AVR at 3 yrs
is 5-fold lower than for the NF/LG pattern
• Important to recognize this entity in order
not to deny surgery to a patient with small
AVA and LG
LF defined as LV stroke volume <35 mL/m2
LG defined as mean trans-aortic pressure gradient < 40 mmHg

21. Echo in Asymptomatic Severe AS -
Discordance between gradient and valve area
• Measurement error
• Small body size
• Paradoxical low flow AS
• Inconsistent grading related to intrinsic
discrepancies in guidelines criteria

22. Measurement errors
• SV and AVA may be underestimated due
to underestimation of LVOT and/or
misplacement of PWD sample volume
• Solution - Several methods can be used to
corroborate the echo measurements of
stroke volume and AVA
• Eg: In absence of significant MR, the SV
can be estimated by Simpson's method

23. Small body size
• Patients with small body size and LV
dimensions may exhibit a lower trans-
valvular pressure gradient because of a
lower although normal stroke volume

24. Paradoxical low flow AS
• Paradoxical LF/LG represents a new
entity in which the LF state results from
both LV concentric remodelling and
reduced subendocardial longitudinal
function
• It’s a true discordance state between
gradient and AVA and is not an
erroneous estimation of AS severity

25. Inconsistent grading related to intrinsic
discrepancies in guidelines criteria
• Combination of clinical, echo & invasive
data, show that a gradient of 40 mmHg
fits more with a valve area of 0.8 cm2
• Valve area of 1 cm2 relates to a mean
gradient of 26 mmHg
• Discordance between AVA (in severe
range) and the gradient (in moderate
range) in patients with preserved LVEF,
a more comprehensive echo evaluation
and other diagnostic tests indicated

26. The Answer to the Dilemma - Individualized
Management
• Clinical factors – poor predictive value
• Confirmation of severity/evaluation of AV
• LV Assessment
• Asymptomatics vs pseudo-asymptomatics
– Exercise test / Exercise stress echo
• True/pseudo-stenosis – Dobu Stress Echo
• Biochemical markers - BNP
• Integration of parameters – Monin risk score

27. Confirmation of Severity of AS
• Severe AS defined as
- mean aortic PG > 40 mmHg
- aortic valve area < 1 cm2 and/or
- peak systolic aortic jet velocity > 4 m/s
• Very severe AS defined as AVA< 0.6 cm2
or indexed AVA< 0.4 cm2 /m2 , Vm>5m/s
[AHA 2014]
• When doubts about severity -
hemodynamic assessment for transvalve
aortic pressure gradient.

28. Peak Aortic Jet Velocity
“An increasing jet velocity predicts a high
likelihood of the need for AVR, the risk of cardiac
death is less well defined” [Senior R. Eur Heart J. May 2012]

29. Rate of Change of Peak Aortic Jet Velocity
• Studies from Otto et al. and Rosenhek et al. have
shown the rate of change of jet velocity is an
important predictor of events
• Increase in jet velocity of >0.3 m/s/year (with a
moderate/heavily calcified valve) had a
particularly poor prognosis [ESC IIA, ACC IIb]
[Rosenhek R. Circulation 2010;121]

30. Aortic Valve Calcification

31. Aortic Valve Calcification (AVC)
• Degree of AVC is a strong predictor of CV events
• Moderate/heavy AVC are a high risk group for
the development of symptoms and need for AVR
• Risk of sudden death in asymptomatics - modest
• Value of AVC in elderly calcific AS will be limited
• EBCT AVC score ≥ 1100 Agaston U showed 93%
sensitivity & 82% specificity for Dx of severe AS
[Senior R. Eur Heart J. May 2012]

32. LV Assessment (LV Mass / Hypertrophy)
• Inappropriately high LV mass (>110% of that
expected for body size, gender) heralded a 4.5
increased risk of mortality independent of other
known risk factors [Cioffi G. Heart 2011;97]
• LVH ≥15 mm (unless this is due to HTN) is a
high risk factor in asymp severe AS (ESC IIb)

33. Asymptomatics vs “Pseudo-asymptomatics”
Exercise Stress Testing
• Uncover symptoms in 40% of “asymptomatics”
• Symptoms with exercise - strongest predictor of
symptom onset (esp <70y) [Das P. Eur Heart J 2005:26]
• In severe asymptomatic AS +ve TMT defined as
- abnormal BP response (fail to rise by 20mm)
[ESC IIa and AHA IIa]
- ST segment changes
- symptoms limiting dyspnea/angina/dizziness
on a modified Bruce protocol [ESC I and AHA I]
- complex ventricular arrhythmias [ESC IIb]
[Sawaya F. CCJM July 2012 vol. 79 7]

34. Exercise Stress Testing
Exercise testing - ACC IIaB
Surgery with + TMT - ACC IIaC / ESC IC

35. Exercise Stress Echocardiography
• Emerging data suggest that exercise stress echo
provides incremental prognostic information in
severe asymptomatic aortic stenosis
• An exercise-induced increase in the AV gradient
>20 mm Hg [Maréchaux S, 2012] or 18 mm Hg
[Lancellotti P, 2005] predicts future cardiac events
• Increase in gradient reflects fixed valve stenosis
with limited valve compliance.

36. Exercise Stress Echocardiography

37. LF/LG Stenosis vs Pseudostenosis (PS)
Dobutamine Stress Echo (DSE)
• When CO is low, AVA calculation is less accurate
- pts with CMP & mild/mod AS → severe AS
• Patients with pseudostenosis have a high risk of
dying during surgical AVR (≈50%), and benefit
more from evidence-based heart failure Rx
• In patients with true stenosis, ventricular
dysfunction is mainly a result of severe stenosis
and should improve after AVR

38. LF/LG Stenosis vs Pseudostenosis (PS)
Dobutamine Stress Echo (DSE)
• DSE → ↑SV in true severe AS → ↑transvalvular
gradient & velocity with minimal change in AVA
• In PS, ↑SV opens AV further → no change in
transvalvular gradient & velocity but ↑ in AVA,
confirming that AS is only mild to moderate

40. Contractile Reserve & Dobutamine Stress Echo
• Contractile reserve (CR) is defined as an ↑more
than 20% in SV during low-dose DSE
• Pts with no CR have a high operative mortality
rate during AVR; but treated conservatively
(65%/5y), they have a much worse prognosis
than AVR (11%/5y) [Tribouilloy C.JACC 2009:53]
• TAVI is an interesting alternative to surg AVR in
this subset of patients [Clavel MA.Circ 2010:122]

41. Brain Natriuretic Peptide Levels
• Levels of BNP ↑ with worsening symptom status
• In severe asymptomatic AS, BNPs may provide
significant prognostic information beyond echo
& clinical analysis [Sawaya F. CCJM July 2012:79(7)]
• Patients with BNP <130 pg/ml / NT-proBNP
<80 pg/ml had a significantly better symptom-
free survival (66% vs 34%) [Bergler-Klein et al]

43. Integration of Risk Markers (Monin Risk Score)
• Values obtained for the score were grouped in
quartiles: Q1 12.9; Q2 14.6; Q3 16.2 and Q4 19.7
• The probability of event-free survival in 20
months was 80% among patients at the first
quartile and only 7% among patients from the
last quartile
• Systematic use of the Monin risk score, still
needs to be validated for routine use

44. Figure 2. Kaplan-Meier analysis of symptom-free survival according to the score quartiles in
the validation cohort.
Monin J et al. Circulation 2009;120:69-75
Copyright © American Heart Association

45. Decision-making in the Elderly Patient
• Operative mortality - 5.7-9% during isolated AVR
• LV conc remodeling, lower SV, ↑LVEDP, & mildly
elevated PAP have a very bad prognosis, with a
mortality of 50.5% at 3.3 yrs [Kahn J. Am Soc Echo 2011]
• One must seek the very-high risk factors, but take
into account: life expectancy x QOL x risk of surg
• Despite high AVR risk, dismal prognosis on
medical Rx & should be referred to surgeon for
an assessment of operative risk or potentially to
cardiologist for TAVI [Sawaya F. CCJM 2012;79(7)]

46. Bhattacharyya S; Hayward C; Senior R. (Jul 2012). Risk stratification in
asymptomatic severe aortic stenosis: a critical appraisal. Eur Heart J

47. Conclusions
• Mgt of severe but asymptomatic AS is challenging
• Abnormal exercise stress & elevated biomarkers
identify a higher-risk group that might benefit
from closer follow up and earlier surgery
• DSE identifies true LF/LG AS amenable for AVR
• Diagnosis of severity should be based on results of
AVA & indexed AVA rather than on gradients
• TAVI will soon become the procedure of choice
where surgery is CI, or even as an alternative to
surgery in other patients at high risk