Asymptomatic Severe Aortic Stenosis – Cardiologist’s Confusion and Surgeon’s Dilemma

Asymptomatic Severe Aortic Stenosis –

Cardiologist’s Confusion and Surgeon’s Dilemma

Dr. Imran AhmedDM. (Cardiology)

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)]

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]

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

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

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]

Benefits of Surgery in Asymptomatic Severe AS [Pellikka et 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

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

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]

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]

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 ??

AVA of 1.0 cm2 yields a gradient of 26 mmHgAVA ≤0.81 cm2 necessary to yield gradient ≥40 mmHg Therefore guidelines per se are inherently inconsistent [Dumesnil JG. Eur Heart J 2010; 31:281–289]

Proposed New Severe AS grading Classification

Miners and Dumesnil et. al.

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 

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 

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 

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

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 

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 

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

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

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

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

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

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

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.

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]

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]

Aortic Valve Calcification

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]

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)

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]

Exercise Stress Testing

Exercise testing - ACC IIaB Surgery with + TMT - ACC IIaC / ESC

IC

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.

Exercise Stress Echocardiography

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

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

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]

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]

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

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

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)]

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

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