The best in heart valve disease Aortic valve stenosis

The best in heart valve disease Aortic valve stenosis Marie Moonen, MD, PhD Heart Valve Clinic, University of Liège, CHU Sart Tilman, BELGIUM My declaration of interest : I have nothing to declare

Prevalence of moderate or severe valve disease (%) HEART VALVE DISEASES Prevalence of AS 10 9 8 7 6 5 4 3 2 1 0 < 44 45-54 55-64 65-74 75 Age (years) Second prevalent heart valve disease in populationbased studies 3-6% of subjects aged over 65 First operated valvular disease in developed countries Mitral regurgitation Mitral stenosis Aortic regurgitation Aortic stenosis Iung et al., Eur Heart J 2003 Nkomo et al., Lancet 2006

Outline of the presentation 1. Aortic valve structure Echocardiographic assessment of AS morphology Aortic valve calcifications Multimodality imaging 2. Imaging in clinical decision making Asymptomatic severe AS Paradoxical low-flow, low-gradient Low-flow, low-gradient 3. New interventions and imaging TAVI : alternative strategy? Multimodality imaging

Aortic valve structure Echocardiographic assessment of AS morphology Essential in patients with AS who are considered for TAVI 2011;108:1589-1599

Accuracy of 2D echo in determining aortic valve structure in patients having AVR for AS TTE has limited accuracy (66%) in determining aortic valve structure Congenitally malformed aortic valves appear to be more likely when : TTE is uninterpretable Heavily calcified valves Parameters interfering with TTE images interpretation : Location rather than amount of calcium Breast tissue High interobserver variability (62%) which increases with severity of AS Biscupid aortic valve is not rare in > 70 years (37%) At present, TEO remains the more precise technique in determining aortic valve structure in patients with AS Ayad et al., Am J Cardiol 2011;108:1589-1599

Aortic valve structure Aortic valve calcifications Pathophysiology of AS? No effective medical treatment Published online Nov 16, 2011

Inflammation-dependent mechanism of calcification Non conventional imaging tools: PET Potential targets for medical therapy Current imaging window using conventional imaging modalities: echo, CT and MRI Aikawa E and Otto CM. Circulation 2011, published online Nov 16 New SE and Aikawa E. Circ Res 2011;108:1381-91

Assessment of valvular calcification and inflammation by PET in patients with AS 121 patients (20 controls, 20 aortic sclerosis, 25 mild AS, 33 moderate AS, 23 severe AS) 18F-FDG (inflammation quantification) and 18F-NaF (calcification detection) tracers 18F-NaF uptake Progressive rise in uptake with increasing disease severity Calcification rather than inflammation appears to be the predominant process 18F-FDG uptake Dweck MR et al., Circulation published online Nov 16

Aortic valve structure Multimodality imaging Valvular anatomic orifice area valvular effective orifice area 2011;13:25

Comparison between CMR and TTE for the estimation of EOA in AS Good agreement between CMR and TTE for the estimation of valve EOA Underestimation of LVOT area by TTE (> LVOT elliptic rather than circular) Overestimation of LVOT VTI by TTE (> flow velocity profile is not flat and is skewed with higher velocities along the anterior and right aspects of the LVOT) Garcia et al., J Cardiovasc Magn Res 2011;13:25

Imaging in clinical decision making Asymptomatic severe AS Medical management? Aortic valve replacement The prognosis of asymptomatic patients is highly variable Risk of rapid stenosis progression Risk of irreversible myocardial damage Increased operative mortality rate in severely symptomatic patients Mortality on the waiting list up to 15% Risk related to delayed symptoms reporting Low event-free survival at 2 years

Imaging in clinical decision making Asymptomatic severe AS Risk stratification is mandatory Valvular calcifications Exercise Doppler echocardiography Peak aortic jet velocity > 4 m/s Inactivity Inappropriately high LV mass Rapid increase in aortic-jet velocity Symptoms during exercise testing BNP Age CAD Renal failure Valvulo-arterial impedance

Imaging in clinical decision making Asymptomatic severe AS 2011;97:301-307

Prognostic effect of inappropriately high LV mass (ilvm) in asymptomatic severe AS Measured LVM = 1.05 [(IVS + PW + LVID d ) 3 LVID d3 ] 13.6 g Calculation of predicted LVM Measured/predicted LVM ratio Cut-off value of 110% of the measured/ predicted LVM ratio to predict outcome with best specificity and sensitivity (ilvm) «Cumulative systolic load dose» indicator IIb class of recommandation for AVR in severe asymptomatic AS (ESC) Cioffi G et al., Heart 2011;97:301-307

Valvulo-arterial impedance (Zva) LV afterload in AS = valvular load + arterial load SV EOA AA Static pressure LVSP P MG SAP } } valvular load total arterial load } load Flow axis LVSP Z va = SVi = MPG + SAP SVi Courtesy of P. Pibarot, Québec Heart and Lung Institute Hachicha et al., Circulation 2007;115:2856-2864

Imaging in clinical decision making Asymptomatic severe AS 2011;108:1463-1469

Prognostic significance of Zva and LV longitudinal function in asymptomatic severe AS 52 patients, NYHA I, AVA 0.4 ± 0.1 cm2, FEVG 61 ± 5% Baseline: Zva closely associated with Long S (r = -0.56, p = 0.016) Follow-up: Long S correlated with EF (r = 0.66, p < 0.001), mass index (r = -0.46, p = 0.015), indexed AVA (r = 0.37, p = 0.04) no correlation between Long S and MPG ROC curves analysis of Zva and LV long S for prediction of events Zito et al. Am J Cardiol 2011;108:1463-

2011;12:850-856 Aortic stiffness index = ln (SBP/DBP) (AoS-AoD)/AoD Independently of the increase of valvular load (= outflow tract obstruction), the increase in arterial load (= proximal aortic stiffness) has a direct detrimental impact on LV function, BNP release and LV filling pressure in patients with asymptomatic severe AS et preserved EF

Imaging in clinical decision making Importance of global afterload in asymptomatic severe AS The afterload imposed by valve stenosis and solely assessed using the mean gradient is unable to predict preclinical changes of myocardial function; An increased global afterload affects myocardial function despite preserved EF; High Zva is associated with LV myocardial dysfunction confirmed by regional LV deformation impairment; High Zva ( 5 mmhg/ml/m 2 ) is associated with reduced cardiac eventfree survival; Contribution of «global afterload» in clinical interpretation of symptoms. Lancellotti et al, EJE 2010; Lancellotti et al, Heart 2010; Hachicha et al, JACC 2009; Zito et al, Am J Cardiol 2011

Imaging in clinical decision making Paradoxical low-flow, low-gradient AS Severe AS based on AVA < 1 cm 2 (< 0.6 cm 2 /m 2 ) Normal LVEF Mean gradient < 40 mmhg? Errors in AVA measurements Wrong cut-off value for severe AS Low flow (SVI < 35 ml/m 2 ) Carabello, NEJM 2002 Dumesnil, EHJ 2010

Severe AS, preserved LV ejection fraction Normal flow, high gradient SVi > 35 ml/m² Mean gradient > 40 mmhg AVA 0.4 ± 0.1 cm/m² LVEDD 48 ± 5 mm Z va = 4.2 ± 0.8 mmhg/ml/m 2 n = 152 (30%) AVR = 80% Low flow, high gradient SVi 35 ml/m² Mean gradient > 40 mmhg AVA 0.3 ± 0.1 cm/m² LVEDD 43 ± 5 mm Z va = 6.0 ± 1.2 mmhg/ml/m 2 n =44 (8%) AVR = 68% Normal flow, low gradient SVi > 35 ml/m² Mean gradient 40 mmhg AVA 0.5 ± 0.1 cm/m² VEDD 48 ± 5 mm Z va = 4.0 ± 0.6 mmhg/ml/m 2 n = 193 (38%) AVR = 53% Low flow, low gradient SVi 35 ml/m² Mean gradient 40 mmhg AVA 0.5 ± 0.1 cm/m² LVEDD 46 ± 5 mm Z va = 5.2 ± 1.3 mmhg/ml/m 2 n =123 (24%) AVR = 36% Dumesnil et al, EHJ 2009

Prevalence of paradoxical low-flow, low-gradient AS Hachicha 2007 Echo 512 pts Barasch 2008 Echo 215 pts Cramariuc 2009 Echo 359 pts Lancellotti 2010 Echo 173 pts Minners 2010 Echo 333 pts Minners 2010 Cath 333 pts Herrmann 2011 Echo 86 pts

Paradoxical low-flow, low-gradient AS LVEF markedly underestimates the extent of myocardial systolic impairment Adda et al., Circ Cardiovasc Imaging published online Nov 22, 2011 Lee et al., JASE 2011

Patients with PLF AS have abnormal myocardial structure and systolic function Moderate AS Severe AS/high gradient Severe AS/low gradient/preserved EF O Severe AS/low gradient/decresed EF Herrmann et al., JACC 2011;58:402-412

Physiopathology of paradoxical low-flow, low-gradient AS LVEF 70 % Classical Normal flow 110 ml Older patients Female gender mean pressure gradient LVEF LVEDVI systemic vascular resistance Paradoxical low-flow LVEF 60 % 90 ml Reduced LV filling Intrinsec myocardial dysfonction Higher global afterload SVI > 35 ml/m² Courtesy of P. Pibarot, Québec Heart and Lung Institute Low flow (SVI 35 ml/m 2 ) Hachicha et al, Circ 2007 SVI 35 ml/m²

Paradoxical low-flow, lowgradient severe AS 2011;123:887-895 A substudy of the SEAS trial

Outcome of patients with low-gradient severe AS and preserved LVEF Letter by Dumesnil and Pibarot in Circulation 2011,124:e360 Low-gradient severe AS : AVA <1.0 cm 2 and MPG < 40 mmhg Moderate AS : 1.0 < AVA < 1.5 and MPG < 40 mmhg Severe AS : AVA < 1.0 cm 2 and MPG > 40 mmhg Jander N et al., Circulation 2011;123:887-895 PLF group : AVA <1.0 cm 2 and MPG < 40 mmhg NF group : AVA < 1.0 cm 2 and MPG > 40 mmhg Potential explanations for these discrepancies : 1. Small body sizes and overestimation of AS severity in PLFLG group due to nonindexed AVA 2. Measurements errors 3. Patients in PLFLG group were not demonstrating the pathognomonic features of the disease (higher LV global hemodynamic load, more severe LV concentric remodeling, smaller cavity size, decreased LV midwall radius shortening) Hachicha et al., Circulation 2007

Paradoxical low-flow, low-gradient severe AS despite preserved LVEF The presence of a moderately increased transvalvular gradient (< 40 mmhg) or velocity (< 4 m/s) does not exclude the presence of severe AS in patients with small AVA and preserved LVEF; Paradoxical low-flow, low-gradient is found in 15 % of AS patients and is often associated with more advanced stage of the disease and worse prognosis; It is important to recognize this entity to avoid to deny surgery to a symptomatic patient with small AVA and low gradient.

Imaging in clinical decision making Low-flow, low-gradient AS AVA < 1 cm² (< 0.6 cm²/m²) with LV dysfunction (EF 40%) And MPG 30 (AHA) 40 (ESC) mmhg Approximatively 20% of AS population Poor outcome under conservative management High operative mortality risk : 8-30%

Imaging in clinical decision making Low-flow, low-gradient AS Does Zva demonstrates the same prognostic value in low-flow, lowgradient AS as it has been previously demontrated among paradoxical low-flow, low-gradient AS? 184 patients, AVA 1 cm2, EF 40%, MPG 40 mmhg 2011;12:358-364

Zva does not improve risk stratification in low EF, low-gradient AS 88 patients (48%) with Zva 5 mmhg/ml/m 2 Based on DES: 12% (15 pts) of pseudosevere AS (DES-induced increased in AVA 0.3 cm 2 associated with peak DES AVA 1 cm 2 ) Zva value similar between true and pseudo-severe AS Follow-up: Zva not predictive of both operative and 5-year postoperative mortality Levy et al., Eur J Echo 2011;12:358-364

Zva does not improve risk stratification in low EF, low-gradient AS LVSP Z va = SVi = MPG + SAP SVi Poor LV function = main determinant of outcome in LF/LG AS Lancellotti P and Magne J. Eur J Echo 2011;12:354-357

New interventions and imaging TAVI : alternative strategy for high-risk patients? Edwards SAPIEN Medtronic CoreValve

Transcatheter versus surgical aortic valve replacement in high-risk patients Smith CR et al. N Engl J Med 2011;364:2187-2198 Placement of Aortic Transcatheter Valves (PARTNER) trial Results for the high-risk subgroup of patients who were still candidates for surgical valve replacement High risk for operative complications or death = risk of death of at least 15% by 30 days after the procedure (based on the STS score) Patients were randomly assigned to undergo either transcatheter or surgical replacement of the aortic valve

TAVI versus surgical AVR in high-risk patients TAVI is similar to AVR with respect to rates of death from any cause at 1 year Smith CR et al. N Engl J Med 2011;364:2187-2198

TAVI versus surgical AVR : a propensity score analysis in patients at high surgical risk Conradi et al., J Thorac Cardiovasc Surg 2011, published online Nov 2

New interventions and imaging Multimodality imaging of the aortic root The optimal strategy for planning TAVI has been expanded : 2D TTE- and catheterization-derived measures have been associated to high variability and significantly underestimation of the aortic annulus dimension. For the crucial measurement of the aortic annulus dimension, multimodal imaging is essential. MRI and TEE provide similar and essential assessment of the aortic valve annulus dimension, especially at the limits of the TAVI range. Close agreement and high reproducibility have been demonstrated between cardiac MRI and CT for the determination of aortic root size. Intra- and interobserver variability is lowest with cardiac MRI. Paelinck B et al., Am J Cardiol 2011;108:92-98 Jabbour et al., JACC 2011;58:2165-2173

New interventions and imaging Multimodality imaging of the aortic root The association between aortic valve/root morphology and outcome after TAVI has been evaluated : The presence and severity of AR after TAVI has been associated with larger aortic annulus dimensions measured with cardiac MRI and CT. Calcifications of the aortic commissures and cusps unless the annulus appear to be responsible for paravalvular leaks. TAVI is associated with good post-procedural valve haemodynamics and clinical outcome in high-risk patients with severe AS and small aortic annulus (< 20 mm). When estimating the effective orifice area of Edwards-SAPIEN valves by Doppler-echo, it is recommended to use the LVOT diameter and velocity measured immediately proximal to the stent. Jabbour et al., JACC 2011;58:2165-2173 Colli et al., J Thorac Cardiovasc Surg 2011;142:1229-1235 Clavel et al., JACC Img 2011;4:1053-1062

Take home messages Aortic valve stenosis «New entity» since etiology and pathophysiology have considerably change Older individuals demontrating diffused manifestations of atherosclerosis (AS, hypertension, ischemic cardiomyopathy) More complexe and multifaceted presentation of the disease

The clinical spectrum of severe AS is more complex that previously believed and includes 3 entities : Pibarot and Dumesnil. JACC 2011;58:413-415

CMR provides a non-invasive and reliable alternative to Doppler-echo for the quantification of AS severity.

Adverse outcome more closely related to Zva and regional myocardial dysfunction than to parameters such as AVA and gradients. LVEF markedly underestimates the extent of myocardial systolic impairment. Low-flow severe AS in presence of preserved EF is a confirmed entity that correspond to a more advanced stage of the disease and require close attention.

Thank you for your attention

2011;32:1542-1550

Longitudinal function Circonferential function Radial function Ng et al., Eur Heart J 2011;32:1542-1550

BNP release according to flow-gradient-valve area Consecutive asymptomatic patients (n=150) with severe AS (AVA<1cm²), preserved LV systolic function (LVEF >55%), normal exercise test Lancellotti et al., JACC 2012 in press

Valve Calcium score Valve Weight Clavel et al. ESC 2010