Aortic stenosis with concomitant mitral regurgitation

Challenges in the evaluation and management of aortic stenosis Aortic stenosis with concomitant mitral regurgitation S1 Philippe Unger, M.D., FESC Erasme Hospital - Université Libre de Bruxelles Brussels, Belgium S2

No conflict of interest

Case #1 72 y-o man Recent onset AF, persistent severe HF despite cardioversion Dobutamine

Low flow low gradient AS SVi 23 ml/m² Ao max V 309 cm/s Ao MPG 25 mm Hg AVA 0.74 cm² Severe organic MR ERO 40 mm² Reg vol 37 ml

MVR CE Magna 31 mm (with chordal preservation) + AVR CE Magna 25 mm preoperative postoperative

Case #2 80 y-o woman, severe aortic stenosis Repeated pulmonary edemas during the last 6 months LVEF 25%

BSA 1.7 m² BP 105/75 mm Hg Max velocity 344 cm/s Mean gradient 26 mm Hg SVI = 20 ml/m² AVA = 0.45 cm² (0.26 cm²/m²) Low flow low gradient AS

ERO 25 mm² Rvol 36 ml

Transcatheter aortic valve implantation (Edwards Sapien 23 mm; transfemoral approach) Pre Post ERO 25 mm²; Rvol 36 ml ERO 6 mm²; Rvol 10 ml

Case #3 78 y-o man, severe aortic stenosis, severe heart failure BSA 1.9 cm² Mean aortic PG 29 mm Hg SVI 20 ml/m² AVA 0.45 cm² Low flow low gradient AS

R =. ERO 17 mm² RV 26 ml

Transcatheter aortic valve implantation (Edwards Sapien XT 26 mm; transapical approach) Pre Post ERO 17 mm² RV 26 ml ERO 21 mm² RV 26 ml

AS + MR: Questions Functional significance? Prognostic value? Does AVR/TAVI affect the severity of MR? Predictors of MR down-grading after AVR/TAVI? Therapeutic strategy?

Prevalence of MR in patients undergoing an isolated aortic valve procedure Aortic valve replacement TAVI Tunick Am J Cardiol 1990 Adams Am J Cardiol 1990 Tassan-Mangina Clin Cardiol 2003 N = 7758 Variable inclusion /exclusion criteria Webb Circulation 2007 Tzikas Cath Cardiovasc Intv 2010 Durst J Heart Valve Diss 2011 N = 950 Organic 50-80% Moazami J Card Surg 2004 Barreiro Circulation 2005 Ruel Circulation 2006 Mainly nonquantitative MR assessement Hekimian JASE 2011 De Chiara Cath Cardiovasc Intv 2011 Samim Int J Cardiol 2011 Mainly nonquantitative MR assessement Caballero-Borrego Eur J Cardiothor Surg 2008 Toggweiler JACC 2012 Waisbren Ann Thor Surg 2008 Wan J Thorac Cardiovasc Surg 2009 Jeong Am J Cardiol 2011 mild: 30-80% moderate: ±15% mild: 70-80% moderate: 20-35% Severe 5-10%

LV remodelling Mitral valve deformation leaflet tethering LV pressure LV-LA pressure gradient Aortic stenosis Mitral regurgitation Functional tolerance Atrial fibrillation Diagnostic challenge Low flow low gradient aortic stenosis forward stroke volume Postop EF Unger P, Lancellotti P, et al. Heart 2010;96:9

Aortic stenosis and mitral regurgitation Functional significance? Prognostic value? Does AVR/TAVI affect the severity of MR? Predictors of MR down-grading after AVR/TAVI? Therapeutic strategy?

Operative Mortality X2 STS Database Euro Heart Survey STS database 2005 http://sts.org/documents/pdf/spring2005sts-executivesummary.pdf Iung B, et al. EuroHeart Survey

Survival Mitral valve repair with AV replacement is superior to double valve replacement 100 % 90 80 79 P=0.01 70 60 50 40 30 72 63 52 46 34 AV replacement and MV repair Double valve replacement 20 10 0 Repair: N=295 Replacement: N=518 2 4 6 8 10 12 14 16 Mean follow-up 6.9±5.9 yrs years Gillinov AM, et al. J Thorac Cardiovasc Surg 2003; 125: 1372

Prognostic significance of moderate versus mild MR before surgical AV replacement A meta-analysis including 17 studies and 3053 patients Nil/mild versus moderate/severe OR/HR CI P Comparative 30-Day mortality 0.41 0.24-0.72 0.002 Comparative 30-Day mortality; Functional MR only 0.38 0.20-0.73 0.004 3 year overall survival 0.49 0.35-0.69 <0.0001 5 year overall survival 0.46 0.34-0.61 <0.00001 10 year overall survival 0.61 0.40-0.92 0.02 Harling L, et al. Eur J Cardiothor Surg 2011;40:1087

Prognostic significance of moderate versus mild MR before TAVI Higher mortality rate @ 30 days No difference after 30 days adjusted HR: 2.10 (1.12-3.94, p = 0.02) 92.5% 86.5% adjusted HR: 0.82 (0.50-1.34, p = 0.42) 83.7% 67.%9 66.2% 58.5% MR mild: n = 319 Moderate: n = 89 Severe: n = 43 Toggweiler, S. et al. J Am Coll Cardiol 2012;59:2068

Aortic stenosis and mitral regurgitation Functional significance Prognostic value Does AVR/TAVI affect the severity of MR? Predictors of MR down-grading after AVR/TAVI? Therapeutic strategy?

Impact of isolated aortic valve replacement on mitral regurgitation First author, Year Aetiology of MR Number of patients Timing of the postop echo Method of MR assessment % of patients with improvement in MR Tunick 1990 Functional + Organic N = 27 mild MR 58 days CFM 67% Adams 1990 Organic + Functional N = 46 mild MR 6 months PW mapping 27% Harris 1997 Functional N=28 mild MR 2.5 months CFM 82% Brasch 2000 Organic + Functional N = 16 moderate MR 2.2 months CFM 44% 16 studies Christenson 2000 Functional N = 58 mild MR 1 week/5 months CFM 46%/60% Tassan-Mangina 2003 Functional N = 23 mild MR 19 days CFM 61% Moazami 2004 Functional N = 80 mild MR > 60 days CFM 45% 1294 patients with MR Functional only (10) or Functional + organic (6) Mostly retrospective Mainly qualitative or ½ quantitative Barreiro 2005 Organic + Functional N = 70 moderate MR Early postoperative CFM 82% if functional 35% if organic Ruel 2006 Functional N = 107 2+ MR 18 months ASE recommendations 44-74% MR assessement Vanden Eynden 2007 Organic + Functional N = 80 moderate MR 1 year CFM and PW Doppler 5-10% 35% mapping, PV flow Caballero-Borrego 2008 Functional N =153 non-severe MR Before discharge CFM and PW, PV flow 72% From OR up to 18 months Waisbren 2008 Functional (No CABG) N = 167 moderate MR Intraoperative Vena contracta width 66% Wan 2009 Functional N=159 moderate MR Discharge ASE recommendations 76% Unger 2008 Organic + Functional N=52 mild MR Early postoperative Matsumura 2010 Functional N=110 moderate MR Early postoperative Improvement 55-65% (27-82%) Deterioration PISA 69% CFM 64% Joo 2011 Functional N=118 mild MR 57 months PISA 72%

postop reduction (%) Quantitative changes in MR after AV replacement 80 70 60 50 40 P<0.0001 vs ERO P=0.034 vs ERO 30 20 10 0 ERO Reg Vol Reg jet/la area Unger, Lancellotti et al. Am J Cardiol. 2008; 102:1378-82

Aortic stenosis and mitral regurgitation Functional significance Prognostic value AVR/TAVI affects the severity of MR Predictors of MR down-grading after AVR/TAVI? Therapeutic strategy?

Predictors of MR down-grading after isolated AVR First author, Year Aetiology of MR Preoperative predictive factors of MR improvement Tunick Am J Cardiol 1990 Functional + organic MR severity Adams Am J Cardiol 1990 Functional + organic None Harris Am J Cardiol 1997 Functional Low LV fractional area, Large left atrial size Brasch Am J Cardiol 2000 Functional + organic LV mass Christenson, Tex Heart Inst J 2000 Functional Presence of coronary artery disease Tassan-Mangina Clin Cardiol 2003 Functional Peak velocity of tricuspid regurgitant jet; Indexed LV mass Moazami J Cardiac Surg 2004 Functional History of previous myocardial infarction Barreiro Circulation 2005 Functional + organic Functional MR Ruel Circulation 2006 Functional No enlarged left atrium (>5cm), no chronic AF No low preoperative peak aortic pressure gradient (< 60 mm Hg) Vanden Eynden Ann Thor Surg 2007 Functional + organic Functional (including ischaemic) MR Caballero-Borrego Eur J CT Surg 2008 Functional Presence of CAD, absence of diabetes and of PHT 17 studies Waisbren Ann Thor Surg 2008 Functional: n=10 Organic + funct: n=7 Functional No CABG MR severity, trace or mild aortic insufficiency Left atrial size < 4.5cm Congestive heart failure Unger Am J Cardiol 2008 Functional + organic MR severity Mitral coaptation height Wan JTCVS 2009 Functional Lesser preop TR, lower MR grade under anesthesia No cerebrovasc disease Lower EF AF Unger Heart 2010 Functional + organic Functional MR; absence of patient-prosthesis mismatch Matsumura Am J Cardiol 2010 Functional Lower tenting area Improvement Joo Ann Thorac Surg 2011 Functional Preoperative RV systolic pressure Functional etiology Low EF, CHF Lower grade of MR under anesthesia Less/no improvement Organic etiology Enlarged atrium Pulmonary HT

Postop RV reduction, ml Postoperative changes in RV (pre-post), ml Relationship between prosthetic EOA and postoperative reduction in mitral regurgitation 30 25 20 15 10 5 0-5 -10 r=0.47; p=0.003 r=0.26, p=ns r=0.47, p=0.003 0.4 0.6 0.8 1.0 1.2 Postop ERO reduction, mm 2 12 10 8 6 4 2 0 25 20 15 6.0±4.0 16±6 2.6±5.0 8.5±8.2 p=0.02 p=0.0025 Projected indexed EOA, cm 2.m -2 10 5 0 N=42 with preoperative ERO 10 mm² No PPM (n=19, 45%) PPM (n=23, 55%) PPM: postop indexed AVA < 0.85 cm²/m² Unger P, Magne J, Lancellotti P. Heart 2010;96:1627

TAVI and MR Webb Circulation 2007 Prosthesis TA/TF Edwards TF Number of pts with MR Etiology of MR 37 NA 1 month 6 months 12 months Timing Improvement Deterioration Predictive factors for improvement 38% 42% 53% NA NA Tzikas Cath Cardiovasc Intv 2010 Gotzmann Am Heart J 2010 Durst J Heart Valve Disease 2011 Hekimian JASE 2011 De Chiara Cathet Cardiovasc Interv 2011 Samim Int J Cardiol 2011 Toggweiler JACC 2012 CoreValve 34 Org 50% 97±47 days 17% 22% Low LVEF CoreValve 34 NA 6 months 44% 21% NA Edwards TF Edwards TF+TA 35 Org 53% (Restrictive MAC) 326 patients Organic in 42-81% 60 Org 74% 7 days 1 month CoreValve 16 Org 81% 7.8 ± 5.4 months Edwards TF+TA Improvement 12-58% 30 months 34% 2% No restrictive MAC 7 days - 1yr 28% 11% LV dilatation Low EF Deterioration 0-33% Functional MR Low EF PAPS<60 mmhg No AF Valve position 12% 33% No low valve (CV) positioning Small LA size 12 Org 42% 1 month 58% 0% Functional MR Edwards 132 Org 45% 1 year 58% 1% Functional MR 40 mm Hg Ao PG No AF NA, data non available

Does the type of prosthesis matter? Prosthesis TA/TF Number of pts with MR Etiology of MR Improvement Deterioration Predictive factors for improvement Timing Webb Circulation 2007 Edwards TF 37 NA 38% 42% 53% NA NA 1 month 6 months 12 months Tzikas Cath Cardiovasc Intv 2010 Gotzmann Am Heart J 2010 CoreValve 34 Org 50% 17% 22% Low LVEF 97±47 days CoreValve 34 NA 44% 21% NA 6 months Durst J Heart Valve Disease 2011 Edwards TF 35 Org 53% (Restrictive MAC) 34% 2% No restrictive MAC 30 months Hekimian JASE 2011 Edwards TF+TA 60 Org 74% 28% 11% LV dilatation Low EF 7 days 1 month De Chiara Cathet Cardiovasc Interv 2011 CoreValve 16 Org 81% 12% 33% No low valve positioning 7.8 ± 5.4 months Samim Int J Cardiol 2011 Edwards TF+TA 12 Org 42% 58% 0% Functional MR 1 month Toggweiler JACC 2012 Edwards 132 Org 45% 58% 1% Functional MR 40 mm Hg Ao PG No AF 1 year NA, data non available

% 100 90 80 70 60 50 40 30 20 10 0 CoreValve vs Edwards prosthesis Impact on MR? P = 0.0003 Improvement P < 0.0001 Deterioration CoreValve (n=84) Edwards (n=276) CoreValve Tzikas, Cath Cardiovasc Intv 2010 Gotzmann, Am Heart J 2010 De Chiara, Cathet Cardiovasc Interv 2011 Edwards Webb, Circulation 2007 Durst, J Heart Valve Disease 2011 Hekimian, JASE 2011 Samim, Int J Cardiol 2011 Toggweiler, JACC 2012

Aortic stenosis and mitral regurgitation Functional significance Prognostic value AVR affects the severity of MR Predictors of MR down-grading after AVR/TAVI? Therapeutic strategy?

2007 ESC Guidelines on the Management of Valvular Heart Disease «Data on multiple valve diseases are lacking and do not allow for evidence-based recommendations..» 2008 Focused Update ACC/AHA 2006 Guidelines for the Management of Patients With Valvular Heart Disease «Each case must be consider individually the committee has developed no specific recommendations.»

When is double-valve surgery indicated in the presence of symptomatic severe AS? when MR is severe however, Some MR improvement may be observed even if there is severe MR when is MR severe?

Treshold of MR severity? Ischaemic (functional) MR ERO 20 mm² (1) Organic MR ERO 40 mm² (2) frequent downgrading after AVR less frequent downgrading risk of future reoperation 25-30 mm² 1. Grigioni F et al. Circulation 2001;103:1759 1764. 2. Enriquez-Sarano M. et al. N Engl J Med 2005;352:875-83

Symptomatic Aortic Stenosis + MR Assess the ERO ERO < 20 mm² ERO 20-29 mm² ERO 30 mm² Functional MR Organic MR PASP > 50 mmhg LAD > 50 mm Atrial fibrillation PPM Yes Low Operative risk+comorbidities Intermediate High No mitral valve surgery No AVR + mitral valve surgery (preferably repair) Isolated AVR Low Intermediate TAVI + MitraClip? TAVI High Surgical Risk adapted from Unger P, Rosenhek R, Lancellotti P. Heart 2011;97:272

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If surgery is indicated because of severe MR, aortic valve replacement will be indicated if: Aortic stenosis Mild moderate severe Jet velocity (m/s) <3 3-4 >4 Mean gradient (mm Hg) <25 25-40 >40 AVA (cm²) >1.5 1-1.5 <1 (<0.6cm²/m²) Indication of AVR Level of evidence Class IIb* C Class IIa B/C Class I C *if evidence that progression may be rapid

Severe Mitral Regurgitation + AS ΔP, jet velocity, AVA Jet velocity <3-4m/s Mean gradient <25 mm Hg AVA >1.5 cm Jet velocity 3-4m/s Mean gradient 25-40 mm Hg AVA 1-1.5 cm² Jet velocity >4m/s Mean gradient >40 mm Hg AVA <1 cm² (<0.6 cm²/m²) ESC ACC/AHA Class III Rapid progression? Class IIb (c) Class IIa (b/c) Class I (c) No aortic valve surgery Aortic valve surgery Operative risk+comorbidities adapted from ACC/AHA and ESC Guidelines on patients with VHD

Severe prosthesis-patient mismatch after aortic bioprosthesis implantation according to the aortic annulus size: PAVI; stentless valve AVR; and stented valve AVR Clavel MA et al. J Am Coll Cardiol. 2009;53:1883

Multivariate Predictors of Reduced MR at 1-Year Follow-Up N = 132 Organic MR: 45% Multivariate Odds Ratio (95% CI) Multivariate p Value Pulmonary pressure <60 mm Hg Absence of atrial fibrillation 2.68 (1.09 6.58) 0.03 2.55 (1.17 5.55) 0.02 Functional MR 2.61 (1.15 5.93) 0.02 Mean gradient 40 mm Hg 2.71 (1.19 6.18) 0.02 Toggweiler, S. et al. J Am Coll Cardiol 2012 Jun 5;59:2068

Prevalence of mitral regurgitation in patients undergoing isolated AVR Authors, Year N Exclusion criteria Method of MR assessment Percentage of patients with preoperative MR Tunick Am J Cardiol 1990 44 None Colour flow mapping 61% with mild MR Adams Am J Cardiol 1990 Tassan-Mangina Clin Cardiol 2003 Moazami J Card Surg 2004 Barreiro Circulation 2005 Ruel Circulation 2006 Caballero-Borrego Eur J Cardiothor Surg 2008 Waisbren Ann Thor Surg 2008 Wan J Thorac Cardiovasc Surg 2009 Jeong Am J Cardiol 2011 10 studies N = 7758 56* None Pulsed wave Doppler mapping 30 Severe AR; unstable haemodynamics Arrhythmia 250 Organic mitral valve disease Previous sternotomy or mitral valve surgery 408 Concomitant bypass surgery Age > 70 y 848 Organic mitral valve disease Patients Variable++ who did not survive the operation organic MVD (6) 577 Organic mitral valve disease moderate Predominant AR AR (3) Predominant coronary artery disease Type CAD/CABG A AD; MR secondary (4) to SAM 227 Organic mitral valve disease Combined procedure (CABG) Endocarditis Right heart valve procedure Moderate or severe AR Colour flow mapping Colour flow mapping Colour flow mapping 2003 American Society of Echocardiography recommendations Colour flow and pulsed wave Doppler mapping, pulmonary vein flow Vena contracta width 4934 Concurrent or previous MVR Color flow mapping, vena contracta or PISA 384 Organic MR Ischemic heart disease Mainly qualitative or 1/2-quantitative Colour flow mapping 82% with 1+ MR 90% with mild MR 78% with mild MR 17.2% with moderate MR 12.6% with 2+ MR mild: 30-80% moderate: ±15% 26.5% with non-severe MR 74% with moderate MR 43% with mild MR 14% with moderate MR 30% with mild MR

Prevalence of mitral regurgitation in patients undergoing TAVI Authors, Year Webb Circulation 2007 Tzikas Cath Cardiovasc Intv 2010 Durst J Heart Valve Diss 2011 Hekimian JASE 2011 De Chiara Cath Cardiovasc Intv 2011 Number of patients MR etiology Method of MR assessment Percentage of patients with preoperative MR 50 NA NA 53% with moderate MR 79 Organic MR 50% Color flow mapping None 24% 57% with mild MR 18% with moderate MR 55 53% MAC with restriction 3% MVP 30% valve thickening 17% functional 254 Organic 68% Functional 32% Vena contracta Color flow mapping VC PISA 63% with mild-to-mod MR 43% with moderate MR 6% with severe MR None 26% 44% with 1+ MR 25% with 2+ MR 5% with 3-4+ MR 58 Organic81% Color flow mapping 72% with 0-1+ MR 22.4% with 2+ MR 5.1% with 3-4+ MR Samim 22 Organic 62,5% NA None 27% 36% with mild MR 32% with moderate MR Mainly Severe in 4% Toggweiler JACC 2012 7 studies N = 950 Organic 50-80% 451 Functional 56% MAC 47% NA; information not available qualitative or 1/2-quantitative ESC/AHA/ACC recommendation mild: 70-80% moderate: 20-35% Severe 5-10% 20% with moderate MR 10% with severe MR

Mitral RV decrease (ml/beat) N=419 EOAi 0.85 cm²/m²: 40.6% MRV decrease PPM=0 MRV decrease PPM=1 Angeloni A, et al. Circ Cardiovasc Imaging 2012;5:36