Sténose aortique à Bas Débit et Bas Gradient

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3.6 m/s Sténose aortique à Bas Débit et Bas Gradient Philippe Pibarot, DVM, PhD, FACC, FAHA, FESC, FASE Canada Research Chair in Valvular Heart Diseases Doctorate Honoris Causa, Université de Liège Institut Universitaire de Cardiologie et de Pneumologie de Québec / Québec Heart & Lung Institute Université LAVAL

Disclosure: Philippe Pibarot Financial relationship with industry: Edwards Lifesciences: Echo CoreLab for PARTNER 2 SAPIEN 3, PARTNER 3, TAVR-UNLOAD, EARLY-TAVR trials V-Wave Ltd: Echo CoreLab for FIM Study Cardiac Phoenix: Echo CoreLab for BACE FIM Study Other financial disclosure: Research Grants from Canadian Institutes of Health Research and Heart & Stroke Foundation of Quebec Off label Use: None

Low Gradient 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 (HFrEF) D2 Stage «PARADOXICAL» LOW-FLOW LOW-GRADIENT (HFpEF) D3 Stage NORMAL-FLOW LOW-GRADIENT D? Stage

Classical Low-Flow, Low-Gradient AS with Reduced LVEF (D2 Stage) HFrEF Form of AS 5-10% of AS population

Classical Low-Flow, Low-Gradient AS LVEF<50%, AVA 1.0, ΔP<40 Low-Dose 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 preferred?

Resting Echo Case #1 DSE LVEF=40% SV= 53 ml P= 49 / 29 mmhg AVA= 0.77 cm 2 LVEF=50% SV= 73 ml P= 92 / 52 mmhg AVA= 0.75 cm 2

Patient Survival (%) Risk Stratification using Flow Reserve 100 126 Patients Group I = flow reserve SV 20% under DSE Group II = no flow reserve 75 Group I, Valve Replacement * 50 Group II, Valve Replacement 25 0 0 Group I, Medical Treatment Group II, Medical Treatment 50 100 Months p= 0.07 vs medical * p= 0.001 vs medical Monin et al, Circulation 2003;108:319-324

1-Year Survival in Classical LF-LG AS according to Contractile/Flow Reserve: TOPAS-TAVI Registry Ribeiro et al. JACC In press

Guidelines Indications for AVR in Classical Low-Flow, Low-Gradient AS Definition: AVA 1.0 cm 2, Mean gradient<40 mmhg, LVEF<50% Stage: D2 Guidelines Recommendation for AVR Class ACC-AHA 2014-2017 ESC-EACTS 2017 ESC-EACTS 2017 AVR is reasonable in symptomatic patients with low LVEF, low-flow/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 AVR should be considered in symptomatic patients with low LVEF, low-flow/low-gradient severe AS with flow reserve on DSE AVR may be considered in symptomatic patients with low LVEF, low-flow/low-gradient severe AS without flow reserve on DSE, particularly when CT calcium scoring confirms severe AS IIa I IIa

Rest SV= 36 ml Q mean =139 ml/s LVEF=20% P= 35 / 22 mmhg AVA= 0.85 cm 2 Case #2 DSE SV= 55 ml Q mean =243 ml/s LVEF=30% P= 63 / 32 mmhg AVA= 1.1 cm 2

Outcome of Patients with Moderate AS and Low LVEF Retrospective 3-center study of 305 patients with moderate AS and LVEF<50% What is moderate AS for a good ventricle may be severe for a depressed ventricle! Van Gils et al. JACC 2017

TAVR UNLOAD Trial Study Design (600 patients, 1:1 Randomized) TAVR UNLOAD Trial International Multicenter Randomized Heart Failure LVEF < 50% NYHA 2 Optimal HF therapy (OHFT) Moderate AS R TAVR + OHFT OHFT Alone Follow-up: 1 month 6 months 1 year Clinical endpoints Symptoms Echo QoL Primary Endpoint Hierarchical occurrence of: All-cause death Disabling stroke Hospitalizations for HF, aortic valve disease Change in KCCQ Reduced AFTERLOAD Improved LV systolic and diastolic function

Rest Case #3 DSE LVEF=25% SV= 45 ml Q=163 ml/s P= 46 / 27 mmhg AVA= 0.8 cm 2 LVEF=30% SV= 46 ml Q=169 ml/s P= 52 / 30 mmhg AVA= 0.8 cm 2

Quantification of AoV Calcification by MDCT: Anatomic Severity of AS Modified Agatston method Calcification is defined as four adjacent pixels with density >130 Hounsfield units None Mild Moderate Severe Clavel et al. European Heart Journal (2016) 37, 2645 2657

Fig. AoV 4 Ca Scoring by MDCT to Differentiate True vs. Pseudo- Severe Stenosis in LF-LGAS Pseudo-Severe True-Severe Case #3 AVC score: 1034 AU AVC density: 220 AU/cm 2 AVC score: 3682 AU AVC density: 980 AU/cm 2 AVC Score: >2000AU in AVC Density: >500 AU/cm 2 in >1200 AU in >300 AU/cm 2 in Clavel et al. JACC 2013

Paradoxical Low-Flow, Low-Gradient AS with Preserved LVEF (Stage D3) HFpEF Form of AS Age Women Hypertension MetS Diabetes 5-15% of AS population Hachicha Z et al., Circulation, 2007 Dumesnil et al. Eur Heart J, 2009 Pibarot & Dumesnil JACC, in press, 2012

Case #4: Paradoxical Low-Flow, Low-Gradient 82 y.o. woman Hypertension treated with ACEI No CAD NYHA III, HF hospitalization LVEF: 65% Global long. strain: 13% Grade II Diastolic Dysf. AS severity on echo: AVA: 0.64 cm 2 ; iava: 0.36 cm 2 /m 2 Doppler velocity index: 0.19 Peak/mean gradient: 44/26 mmhg SV index: 29 ml/m 2

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 2017 AVR should be considered in symptomatic patients with low flow, low gradient (<40 mmhg) AS with normal EF after careful confirmation of severe AS. IIa ACC-AHA 2014/2017 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

2017 ESC-EACTS Guidelines Baumgartner et al. EHJ 2017

Criteria that increase the likelihood of severe AS in patients with Low Gradient AS and Preserved LVEF Baumgartner et al. EHJ 20917 Pseudo-Severe True-severe

Case #4: Aortic Valve Calcium Scoring by MDCT AVC Score: 3200 AU

Case #5: Normal-Flow, Low-Gradient AS (? Stage) Clavel et al. JACC Img. 2017;10:185 202

Potential Causes of Normal-Flow, Low-Gradient AS Measurement errors: overestimation of stroke volume or underestimation of gradients Normal stroke volume index ( 35 ml/m 2 ) but low mean transvalvular flow rate (Q mean = SV/LVET < 200 ml/s) : e.g. bradychardia % Pts with NF-LG Systemic arterial hypertension and/or reduced arterial compliance Inconsistency in the guidelines criteria Cote et al. JAHA 2017

Normal-Flow, Low-Gradient AS In normal flow conditions: An AVA of 1.0 cm 2 corresponds to a mean gradient of ~30-35 mmhg An AVA of 0.8 cm 2 corresponds to a mean gradient of ~40 mmhg Minners et al. Eur Heart J, 2008 Berthelot-Richer et al. JACC Img; 2016

MODERATE AS SEVERE AS VERY SEVERE AS 100% SAS HIGH GRADIENT AS 60-70% SAS PARADOXICAL LOW-FLOW, LOW-GRADIENT AS 40-50% SAS NORMAL-FLOW, LOW-GRADIENT AS

Outcome and Impact of AVR in Low-Gradient AS: A Meta-Analysis 18 studies, 7,459 patients Paradoxical LF-LG AS: - Increased risk of mortality compared to moderate AS and high-gradient AS - Outcome is improved by AVR Normal Flow, Low-Gradient AS: - Outcome similar to high-gradient AS but improved by AVR Dayan JACC; 66:2594-03, 2015

Effect of Initial AVR on Prognosis of Patients with HG and LG AS: The Current Registry (n=2097) Composite of AoV related death or HF Rehospitalization High Gradient (AS) Low Gradient (PLF & NF) AS Taniguchi et al Circ CV Int. 2017

Take Home Messages In symptomatic low gradient AS, confirm: 1- Accuracy of measurements 2- Flow/LVEF Status 3- AS severity Clavel et al. JACC Img. 2017;10:185 202

4- Select Type of AVR in Low-Gradient AS Clavel et al. JACC Img. 2017;10:185 202

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