Low Gradient Severe? AS
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1 Low Gradient Severe? AS Philippe Pibarot, DVM, PhD, FACC, FAHA, FESC, FASE Canada Research Chair in Valvular Heart Diseases Institut Universitaire de Cardiologie et de Pneumologie de Québec / Québec Heart & Lung Institute Université LAVAL
2 Disclosure Statement - Edwards LifeSciences: Echo CoreLab for the PARTNER-II SAPIEN 3 - V-Wave: Echo CoreLab for FinM Experience
3 LOW GRADIENT SEVERE? AS AVA 1.0 cm 2 MG<40 mmhg <50% LVEF >50% SVi <35 ml/m 2 >35 ml/m 2 «CLASSICAL» LOW-FLOW LOW-GRADIENT D2 Stage «PARADOXICAL» LOW-FLOW LOW-GRADIENT D3 Stage NORMAL-FLOW LOW-GRADIENT D? Stage
4 NORMAL-LVEF «PARADOXICAL» LOW-FLOW LOW-GRADIENT LOW-LVEF «CLASSICAL» LOW-FLOW LOW-GRADIENT LVEF=60% SV=46 ml MG=29 mmhg LVEF=25% SV=42 ml MG=25 mmhg
5 Low-Flow, Low-Gradient Severe(?) AS True-Severe AS Pseudo-Severe AS Low Flow Normal Flow Low Flow Normal Flow AVA P Gradient = Q 2 K AVA 2
6 Classical Low-Flow, Low-Gradient AS with Reduced LVEF LVEF=25% SV=42 ml MG=25 mmhg
7 LVEF 50% AVA 1.0 ΔP<40 Dobutamine-Stress Echo SV 20 % Contractile (Flow) Reserve SV < 20 % No Contractile (Flow) Reserve ΔP 40 AVA 1.0 True-Severe AS ΔP<40 AVA>1.0 Pseudo-Severe AS No AS Severity: Indeterminate MSCT: AoV Ca Score >1200 >2000 Yes True-Severe AS SAVR ± CABG TAVR ± PCI HF Therapy SAVR (High Op. Risk) TAVR? BAV+TAVR?
8 2014 ACC/AHA Guidelines on Management of VHD: Indications for AVR in AS Definition: AVA 1.0 cm 2, Mean gradient<40 mmhg, LVEF<50% Stage: D2 Recommendation AVR is reasonable in symptomatic patients with low LVEF, lowflow/low-gradient severe AS with a DSE that shows a mean gradient 40 mm Hg with an AVA 1.0 cm 2 at any dobutamine dose Class Level IIa B Nishimura, Otto et al. JACC 2014
9 2012 ESC/EACTS Guidelines on Management of VHD: Indications for AVR in AS Severe AS on DSE: Increase in AVA <0.2 cm 2 with final AVA <1 cm 2 ; mean gradient >40 mmhg Flow reserve: >20% increase in stroke volume Vahanian et al. EHJ 2012
10 Resting Echo Case DSE LVEF=40% SV= 53 ml AVA= 0.77 cm 2 P= 49 / 29 mmhg LVEF=50% SV= 73 ml AVA= 0.75 cm 2 P= 92 / 52 mmhg
11 Case: Contractile/flow reserve: Yes Stenosis severity: True-severe
12 Resting Echo Case DSE LVEF=25% SV= 51 ml AVA= 0.8 cm 2 P= 46 / 27 mmhg LVEF=30% SV= 57 ml AVA= 0.8 cm 2 P= 52 / 30 mmhg
13 Case: Contractile/flow reserve: No Stenosis severity: Indeterminate
14 Fig. Usefulness 4 of AoV Ca Scoring by MDCT to Differentiate True vs. Pseudo- Severe Stenosis in Low-Flow, Low-Gradient AS Pseudo-Severe True-Severe AVC: 1034 AU AVC: 4682 AU Clavel et al. JACC 2013: AVC Score to identify Severe AS: >1200AU in >2000 AU in
15 Fig. 4 Mayo-Québec-Bichat Collaboration: Accuracy of AVC to identify severe AS Sensibility, (%) Gender Threshold AUC Sensitivity (%) Specificity (%) PPV (%) Women 1274 AU Men 2065 AU Clavel et al. JACC Specificity, (%) Case: 2010 AU NPV (%)
16 Mayo-Québec-Bichat Collaboration: Impact of AVC on Survival In patients with AS >1200AU in >2000 AU in Whole Cohort Patients treated Medically Clavel et al. JACC 2014
17 LVEF=60% SV=46 ml MG=29 mmhg Paradoxical Low-Flow, Low-Gradient AS with Preserved LVEF Age Women Hypertension MetS Diabetes
18 82 y.o. woman Hypertension treated with ACEI No CAD NYHA III, HF hospitalization LVEF: 65% Severe Diastolic Dysf. AS severity on echo: AVA: 0.64 cm 2 ; iava: 0.36 cm 2 /m 2 Peak/mean gradient: 44/26 mmhg SV index: 29 ml/m 2 Case
19 Pronounced Concentric Remodeling Constrictive Pericarditis AORTIC STENOSIS ± HYPERTENSION Impaired Diastolic Filling Impaired Longitudinal systolic function Atrial Fibrillation Mitral Stenosis Mitral Regurgitation Tricuspid Regurgitation Reduced Forward Stroke Volume (SVi<35 ml/m 2 ) Reduced Transvalvular flow rate Low-Flow, Low-gradient AS Despite Preserved LVEF Pibarot & Dumesnil, Circulation 2013
20 Survival by stroke volume index in patients with low-gradient normal LVEF severe aortic stenosis Eleid et al. Heart 2014
21 Outcome of Patients with Paradoxical Low-Flow, Low-Gradient AS 150 Pts with asymptomatic severe (AVA<1.0 cm 2 ) AS LVEF>50% Lancellotti P, Magne J et al. J Am Coll Cardiol. 59:235 43, 2012
22 Outcome of Patients with Low-Gradient AS Eleid et al. Circulation 2013
23 Outcome in Paradoxical Low-Flow, Low-Gradient Severe Aortic Stenosis and Preserved LVEF A Cardiac Catheterization Study Mohty et al. Circulation 2013
24 Outcome of Patients with Paradoxical Low-Flow, Low-Gradient AS Case Match Study: patients Clavel et al. JACC 2012
25 Outcome of Patients with Paradoxical Low-Flow, Low-Gradient AS Conclusions: Patients with paradoxical LFLG AS exhibit marked concentric remodelling, impaired LV longitudinal function and worse prognosis Normal-flow, low-gradient AS patients have outcomes similar to moderate AS Mehrota et al. Eur Heart J 2013
26 Impact of AVR on Survival in Patients with Paradoxical Low-Flow, Low-Gradient AS Clavel MA JACC in press Clavel et al. JACC 2012 Tarantini et al. Ann Thorac Surg, 91: , 2011
27 Impact of AVR on Outcome of Symptomatic Patients with Severe Stenosis, Low Gradient, and Preserved LVEF 1704 Patients Eleid et al. Circulation 2013
28 Outcome of Patients With Low-Gradient "Severe" Aortic Stenosis and Preserved LVEF A Substudy of the SEAS trial AVA<1.0 ΔP<40 AVA: ΔP<40 AVA<1.0 ΔP>40 Jander et al. Circulation. 2011;123:
29 Outcome of Patients with Paradoxical Low-Gradient AS and Impact of AVR Tribouilloy et al. JACC;
30 Outcome of Patients with Paradoxical Low-Gradient AS and Impact of AVR HG-SAS, AVR PLG-SAS PLG-SAS, AVR PLG-SAS, No AVR HG-SAS HG-SAS, No AVR Maes et al., Circ Imaging April 2014
31 Potential Causes of Discordance between AVA (e.g. 0.8) and gradient (e.g. 30) in Pts. With Preserved LVEF Measurement errors Small body size Normal-flow, low-gradient AS Inconsistency in guidelines criteria Paradoxical low-flow, low-gradient severe? AS Minners et al. Eur Heart J, 2008
32 Outcome of Low-Flow / Low-Gradient AS: A Meta-Analysis
33 Benefit of AVR in Low-Flow / Low-Gradient AS: A Meta-Analysis Low-Flow Low Gradient HR: 044 [ ] Normal-Flow Low Gradient HR: 048 [ ] Low Gradient (Normal and Low flow) HR: 044 [ ] High Gradient HR: 025 [ ]
34 Treatment Comparison in Normal EF, Low-flow, low-gradient AS 90% 80% 70% LF NEF LG A - TAVR LF NEF LG A - Surgery LF NEF LG B - TAVR LF NEF LG B - Std Rx log rank p= % 2-Year Death (%) 60% 50% 40% 30% 20% 10% 56.5% 41.1% 39.7% 0% Numbers at Risk Days A TAVR A Surgery B TAVR B Std Rx Herrmann et al. Circulation 2013
35 Guidelines on Management of VHD: Indications for AVR in Paradoxical Low-Flow, Low-Gradient AS Definition: AVA 1.0 cm 2, Indexed AVA 0.6 cm 2 /m 2 Mean gradient < 40 mmhg, LVEF 50%, SVi<35 ml/m 2 Stage: D3 Guidelines Recommendation for AVR Class ESC-EACTS 2012 AVR should be considered in symptomatic patients with low flow, low gradient (<40 mmhg) AS with normal EF only after careful confirmation of severe AS. IIa ACC-AHA 2014 AVR is reasonable in symptomatic patients who have low-flow, low-gradient severe AS who are normotensive and have an LVEF 50% if clinical, hemodynamic, and anatomic data support valve obstruction as the most likely cause of symptoms Vahanian et al. EHJ 2012 Nishimura, Otto et al. JACC 2014 IIa
36 Usefulness of Stress-Echocardiography to Differentiate True vs. Pseudo- Severe Stenosis in Paradoxical, Low-Flow, Low-Gradient AS REST DSE 15 µg/kg/min 51 patients with PLF-LG Peak ΔP: 51 Mean ΔP: 29 AVA: 0.70 LVEF: mmhg 57 mmhg 0.77 cm 2 65% Clavel et al. JACC Imaging 2013
37 Case: Aortic Valve Calcium Scoring by MDCT AVC Score: 3200 AU
38 JACC;
39 PARADOXICAL LOW-GRADIENT AS MG<40 mmhg AVA<1.0 cm 2 AVAi<0.6 cm 2 /m 2 LVEF>50% Reassess STEP #1: Measurement Error? No Corroborate measurements of SV, AVA, MG by other methods Identify causes of Low Flow PARADOXICAL LOW-FLOW, LOW-GRADIENT AS STEP #2: Low Flow (SVi<35 ml/m 2 )? Yes STEP #3: Symptoms? No No NORMAL-FLOW, LOW-GRADIENT AS CLOSE FOLLOW-UP Yes Anti-hypertensive Therapy Yes Rule out pseudo-severe AS: - AoV Calcium by MDCT - Dobutamine Stress Echo STEP #4: Hypertension? No STEP #5: Stenosis Severity? True-Severe Pseudo- Severe SURGICAL OR TRANSCATHETER AVR (Class IIa)
40
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