Asymptomatic Severe Aortic Stenosis – Cardiologist’s Confusion and Surgeon’s Dilemma
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Transcript of Asymptomatic Severe Aortic Stenosis – Cardiologist’s Confusion and Surgeon’s Dilemma
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Asymptomatic Severe Aortic Stenosis –
Cardiologist’s Confusion and Surgeon’s Dilemma
Dr. Imran AhmedDM. (Cardiology)
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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)]
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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]
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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
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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
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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]
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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
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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
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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]
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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]
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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 ??
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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]
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Proposed New Severe AS grading Classification
Miners and Dumesnil et. al.
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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.
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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]
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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]
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Aortic Valve Calcification
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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]
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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)
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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]
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Exercise Stress Testing
Exercise testing - ACC IIaB Surgery with + TMT - ACC IIaC / ESC
IC
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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.
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Exercise Stress Echocardiography
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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
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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
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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]
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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]
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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
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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
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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)]
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Bhattacharyya S; Hayward C; Senior R. (Jul 2012). Risk stratification in asymptomatic severe aortic stenosis: a critical appraisal. Eur Heart J
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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
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