Prof. Patrizio LANCELLOTTI, MD, PhD Heart Valve Clinic, University of Liège, CHU Sart Tilman, Liège, BELGIUM

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The Patient with Aortic Stenosis and Mitral Regurgitation Prof. Patrizio LANCELLOTTI, MD, PhD Heart Valve Clinic, University of Liège, CHU Sart Tilman, Liège, BELGIUM

Aortic Stenosis + Mitral Regurgitation?

Etiology of MR in patients with significant aortic valve disease Functional LV dysfunction «Ischemic» MR or not Mixed Organic Intrinsic MV dysfunction Rheumatic heart disease Myxomatous degeneration Chordal/papillary muscle rupture Calcifications of mitral leaflets or annulus Undetermined

Pathophysiology LV remodelling Mitral valve deformation 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 Impedes detection of subclinical myocardial dysfunction EF Unger et al. Heart 2010;96:9-14

AVA 0.65 cm² (0,34 cm²/m²) LVOT diameter 2,2 cm Stroke volume 35 ml (18 ml/m²)

Prevalence 10% of all cardiac procedures 5% of all AVR +/-1000/yr STS database 2005 http://sts.org/documents/pdf/spring2005sts-executivesummary.pdf

Prevalence of MR in patients undergoing isolated AVR Authors, Year Tunick Am J Cardiol 1990 Adams Am J Cardiol 1990 9 studies 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 Number of patients Exclusion criteria Method of MR assessment Percentage of patients with preoperative MR 44 None Colour flow mapping 61% with mild MR 56* None Pulsed wave Doppler mapping 82% with 1+ MR 30 Severe AR Unstable haemodynamic state Arrhythmia 250 Organic mitral valve disease Previous sternotomy or mitral valve surgery N=2550 Variable 408 Need for concomitant bypass surgery Age > 70 y 848 Organic mitral valve disease Patients who did not survive the operation 577 Organic mitral valve disease Predominant AR Predominant coronary artery disease Type A aortic dissection MR secondary 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 organic MVD (4) Echocardiography recommendations moderate AR (3) CAD/CABG (4) Qualitative or semi-quantitative Colour flow and pulsed wave Doppler mapping, pulmonary vein flow Vena contracta width 90% with mild MR 78% with mild MR 17.2% with moderate MR mild: 12.6% with 60-80% 2+ MR moderate: ±15% 26.5% with non-severe MR 74% with moderate MR

Risk associated with double valve replacement STS database 2005 http://sts.org/documents/pdf/spring2005sts-executivesummary.pdf

Euro Heart Survey Operative mortality and morbidity of interventions according to the underlying valve disease Aortic stenosis n=512 Multiple valve disease n=185 Aortic stenosis n= Multiple valve dis 12 10 % 8 6 4 2 mponnade Embolism Mediastinitis 0 Mortality Major bleeding Tamponnade Embolism Mediastinitis Iung et al. Eur Heart J 2003; 24:1231

Long-term outcome after aortic + mitral valve replacement Independent predictors of late outcome: Age LVEF Additional tricuspid surgery NYHA class CAD requiring CABG Turina, J. et al. Circulation 1999;100:II-48-II-53

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

AVR + MV repair vs AVR + AVR replacement/ event-free survival AVR + MV repair p < 0.001 AVR + MVR Talwar S, et al Ann Thorac Surg. 2007:84:1219

Prognostic impact of MR in patients undergoing isolated AVR Functional MR First author, Year Absil, Eur J Cardiothoracic Surgery 2003 Number of patients with MR 2 Aetiology of MR Prognostic value 58 Functional No significant prognostic value Ruel, Circulation 2006 107 Functional No significant effect on mortality Wan, JTCVS 2009 190 Functional No independent prognostic value Caballero-Borrego, Eur J Cardiothoracic Surgery 2008 155 Functional Independent risk factor for mortality and morbidity Age, diabetes, renal failure, LV dysfunction, Atrial fibrillation

Prognostic impact of MR in patients undergoing isolated AVR Organic MR First author, Year Number of patients with Aetiology of MR Prognostic value MR 2 Barreiro, Circulation 2005 Takeda, Eur J Cardio Surg 70 Organic (2/3) Functional (1/3) 59 Organic (2/3) Functional (1/3) Independent risk factor for longterm mortality Independent risk factor for longterm morbidity

Independent Predictors of Late Mortality as Determined by Multivariate Statistical Analysis Barreiro, C. J. et al. Circulation 2005;112:I-443-I-447

First author, Year Tunick 1990 13 studies Adams 1990 Aetiology of MR Functional Organic Organic Functional Number of patients Timing of the postoperative echo examination Method of MR assessment % of patients with improvement in MR N = 27 with mild MR 58 days CFM 67% N = 46 with mild MR 6 months PW Doppler mapping 27% Harris 1997 Functional N=28 with mild MR 2.5 months CFM 82% Brasch 2000 N = 16 with moderate MR Christenson 2000 Functional N = 58 with mild MR 1 week and 5 months Tassan-Mangina 2003 Functional in all except 2 patients 2.2 months CFM 44% CFM 46% and 60% N = 23 with mild MR 19 days CFM 61% Moazami 2004 Functional N = 80 with mild MR > 60 days CFM 45% Barreiro 2005 Organic Functional N = 70 with moderate MR Early postoperative CFM 82% if functional 35% if organic Ruel 2006 Functional N = 107 with 2+ MR 18 months 2003 ASE recommendations Vanden Eynden 2007 Caballero-Borrego 2008 Waisbren 2008 Impact of isolated AVR on MR Functional: 8 Organic Functional + Functional organic: 5 Organic Functional Functional Functional No CABG 1014 patients mild or moderate MR N = 80 with moderate MR N =153 with non-severe MR N = 60 mild MR N = 167 moderate MR Wan 2009 Functional N=159 with moderate MR From OR up to 18 months 1 year CFM and PW Doppler mapping, PV flow Before hospital discharge CFM and PW Doppler mapping, PV flow 44-74% 35% 72% Intraoperative Vena contracta width 66% of preop. moderate MR Discharge Qualitative or ½ quantitative studies All retrospective studies except one 2003 ASE recommendations 65-75% (27-82%) 76%

Quantitative changes in MR after isolated AVR Unger P et al. Am J Cardiol. 2008; 102:1378-82

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

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 in all except 2 patients Peak velocity of tricuspid regurgitant jet Indexed Functional LV mass etiology Moazami J Cardiac Surg 2004 Functional History of previous myocardial infarction Barreiro Circulation 2005 Functional + organic Functional MR 14 studies 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 Waisbren Ann Thor Surg 2008 Functional: n=8 Organic + funct: n=6 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 Improvement Low EF, CHF Lower grade of MR under anesthesia Less MV deformation Less/no improvement Organic etiology Enlarged atrium AFib Pulmonary HT Wan JTCVS 2009 Functional Lesser preop TR, lower MR grade under anesthesia No cerebrovasc disease Lower EF

Changes in hemodynamic and echocardiographic data according to mitral regurgitation etiology Functional MR Organic MR P value Variables (n=20, 48%) (n=22, 52%) LV geometry and function Indexed LVED volume, ml 12±13 4±7 0.01 Indexed LVES volume, ml 9±12 4±6 NS Indexed LV mass, g.m -2 9±25 5±26 NS LV ejection fraction, % -4±11-5±8 NS Mitral regurgitation Effective regurgitant orifice, mm 2 5.8±5.2 2.8±4.3 0.04 Regurgitant volume, ml 14.5±7 9.3±8.2 0.03

Preop Predictors of Persistent Functional MR >1.4 cm² 0.7 cm 9.7 cm² Matsumura Y et al. Am J Cardiol. 2010; 106: 701-706

Relationship between postoperative changes in mitral tenting area and reduction in mitral regurgitation in patients with functional MR 25 Changes in ERO (pre-post), mm 2 35 Changes in RV (pre-post), ml 20 30 15 10 25 20 15 5 10 0-5 r=0.51 p=0.025-10 -1.5-1.0-0.5 0 0.5 1.0 1.5 2.0 5 0-5 r=0.55 p=0.02-10 -1.5-1.0-0.5 0 0.5 1.0 1.5 2.0 Postoperative changes in mitral tenting area, cm 2

Postoperative improvement Postoperative changes in MR according to the presence/absence of patient/prosthesis mismatch PPM: postop indexed AVA < 0.85 cm²/m² in ERO, mm 2 12 10 8 6 4 6.0±4.0 p=0.02 2.6±5.0 2 0 No PPM (n=19, 45%) PPM (n=23, 55%) Unger P et al. (Abstract) Circulation. 2009;120:S768

Relationship between aortic projected indexed EOA and reduction in ERO (preop minus postop value) 20 A Postoperative changes in ERO (pre-post), mm 2 15 10 5 0-5 -10 r=0.14, p=ns r=0.14, p=ns Projected indexed EOA, cm 2.m -2 r=0.70, p=0.0003 r=0.70, p=0.0003 r=0.44, p=0.01 Functional MR MR Organic Organic MR MR 0.4 0.6 0.8 1.0 1.2

When is double-valve surgery indicated? ACC/AHA 2006 Guidelines for the Management of Patients With Valvular Heart Disease «Remarkably few data exist to objectively guide the management of mixed valve disease Hence, each case must be consider individually the committee has developed no specific recommendations.» 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.»

When is double-valve surgery indicated? If MR is severe however, There are data on 40 patients with severe MR who did not undergo surgical mitral valve intervention 90% of them had an improvement of at least one grade When is MR considered severe?

Threshold of MR severity? Ischaemic (functional) MR 20 mm² (1) Organic MR 40 mm² (2) frequent downgrading after AVR less frequent downgrading risk of future reoperation 30 mm² 1. Lancellotti et al. Circulation 2005 2. Enriquez-Sarano M. et al. N Engl J Med 2005

When is double-valve surgery (not) indicated? Assessment of MR severity (ERO) Knowledge of functional or organic aetiology Suitability for MV repair Operative risk and comorbidities

Surgical Risk ERO < 20 mm² Symptomatic Aortic Stenosis + MR ERO 20-29 mm² ERO 30 mm² Functional MR Organic MR PASP > 50 mmhg LAD > 50 mm Atrial fibrillation PPM MV deformation No No mitral valve surgery Yes Low AVR + mitral valve surgery (preferably repair) Operative risk+comorbidities Intermediate Isolated AVR High Percutaneous aortic valve implantation Low Intermediate High