Ioannis Alexanian, MD, PhD Department of Cardiology General Hospital of Chest Diseases Sotiria Athens

MITRAL REGURGITATION IN PATIENT WITH SEVERE AORTIC VALVE STENOSIS Ioannis Alexanian, MD, PhD Department of Cardiology General Hospital of Chest Diseases Sotiria Athens

I HAVE NOTHING TO DECLARE

Management of severe aortic stenosis Guidelines on the management of valvular heart Disease ESC 2012 European Heart Journal (2012) 33, 2451 2496

Aortic valve and double-valve replacement in the last 10 years Nombela-Franco L. et al J Am Coll Cardiol 2014;63:2643 58

THE FUTURE OF TRANSCATHETER AORTIC VALVE IMPLANTATION Germany European Heart Journal (2016) 37, 803 810

MITRAL REGURGITATION Etiology Mechanisms - Assessment

Dal-Bianco J. et al. Can J Cardiol. 2014 September ; 30(9): 971 981

Causes and mechanisms of mitral regurgitation Mechanism Organic Functional Cause Non-ischemic Degenerative (annular calcification, flail leaflets); Rheumatic; Endocarditis; Iatrogenic (drugs, radiation); Inflammatory (lupus, endomyocardial fibrosis ); Traumatic (rupture papillary muscle or chord) Cardiomyopathy; Myocarditis; Any cause of left ventricular remodelling Ischemic Rupture papillary muscle Functional ischemic J Am Coll Cardiol 2014;63:2643 58

Heterogeneity of FMR

Echocardiography assessment of MR severity: main approaches Method Recording technique/equation Strengths Limitations Colour jet area Vena contracta width PISA method Apical image, includes LA Nyquist limit 50 60 cm/s Trace maximum regurgitant jet MR jet/la area Colour flow through the MV in PLAX or apical 4C view Identify the image with maximal flow through the valve VCW is the narrowest region of the regurgitant jet Apical 4C view / Mid systole Nyquist limit 15 40 cm/s Peak CW MR velocity EROA=2πr 2 Va/peak MRV RVol=EROA VTIMR MR screening Simple method Independent of haemodynamics, pressure and flow rate Independent of haemodynamics, pressure and flow rate Preferred quantitative approach Dependent on technical and haemodynamic factors Correlation with severity is poor Not recommended to quantify severity Low colour gain, poor acoustic window, failure to assess multiple jets, non-circular EROA: underestimate VCW High colour gain, AF: overestimate VCW Dynamic behaviour of MR Assumption of a hemispheric shape and a circular EROA Dynamic behaviour of MR Volumetric method Apical 4C view/apical 5C view PW at the MV/PW at the LVOT Mitral annulus diameter/lvot diameter Mitral inflow volume=mv d 0.785 VTIMV LVOT volume=lvot d 0.785 VTILVOT RVol=mitral inflow volume LV outflow volume RF=RVol 100/mitral inflow volume EROA=RVol/VTIMR Integration of the systolic behaviour of MR Alternative method if PISA or VCW are not accurate or applicable Time consuming Inaccurate if significant AR Less reproducible Not recommended as first line method 3D echocardiography Full volume colour Doppler or 3D zoom acquisitions of the MR jet: dataset cropping with MPR tools for evaluation of VCA Diagnosis of location and extent of disease No geometrical assumptions Functional MR, multiple or eccentric jets Poor acoustic window Poor spatial and temporal resolution of live acquisition of 3D colour Doppler Off line manipulation Dynamic behaviour of MR Zamorano ZL et al. Heart. 2015 Jan;101(2):146-54

Echocardiographic evaluation of mitral regurgitation severity Mild Moderate Severe Specific signs Central jet Small (<4 cm²) MR more than mild large LA area <10% of LA but no criteria for >40% of LA VCW <0.3cm severe MR 0.7 cm Flow convergence No or minimal Large Systolic reversal in No Yes pulmonary veins Supportive signs A-wave dominance MR more than mild E wave >1.5m/s Doppler MR signal Low-density but no criteria for High-density LV and LA size Normal severe MR Enlarged Quantitative parameters RVol (ml/beat) <30 30-59 60 RVol (ml/beat) in FMR* 30 RF (%) <30 30-49 50 ERO (cm²) <0.20 0.20-0.39 0.40 ERO (cm²) in FMR* 0.20 J Am Coll Cardiol 2014;63:2643 58

Proposed algorithm for primary MR severity assessment with echocardiography Zamorano ZL et al. Heart. 2015 Jan;101(2):146-54

Pathophysiology of concomitant mitral regurgitation in aortic stenosis European Heart Journal (2014) 35, 2627 2638

SURGICAL AORTIC VALVE REPLACEMENT (SAVR) IN THE PRESENCE OF SIGNIFICANT MR

Guidelines on the management of valvular heart Disease ESC 2012 When MR is associated with severe AS, its severity may be overestimated in the presence of the high ventricular pressures and careful quantification is required. As long as there are no morphological leaflet abnormalities (flail or prolapse, postrheumatic changes, or signs of infective endocarditis), mitral annulus dilatation or marked abnormalities of LV geometry, Surgical intervention on the mitral valve is in general not necessary and non-severe secondary MR usually improves after the aortic valve is treated. European Heart Journal (2012) 33, 2451 2496

Changes in Moderate Mitral Regurgitation (Functional Etiology) After Surgical Aortic Valve Replacement J Am Coll Cardiol 2014;63:2643 58

Effects of Valve Replacement for Aortic Stenosis on MR After surgery, there was a decrease in the average individual percentage decrease in: ERO (25%± 46%) RV(40%± 41%) the ratio of the regurgitant jet to left atrial area (37% ± 38%). The difference in reduction was significant between ERO and RV (p<0.0001) and between ERO and the ratio of regurgitant jet to left atrial area (p= 0.034)

Aortic Valve Replacement and Concomitant Mitral Valve Regurgitation in the Elderly 408 consecutive elderly patients underwent isolated AVR and were stratified into no/mild MR (Group I; n=338) versus moderate MR (Group II; n= 70) Moderate MR was an independent risk factor impacting long-term survival MR persisted or worsened in 65.4% of patients with intrinsic mitral valve disease (myxomatous, calcific, or ischemic MR) MR improved in 81.8% of functional MR patients Barreiro C. et al. Circulation. 2005;112 [suppl I]:I-443 I-447

Effect of Aortic Valve Replacement for Aortic Stenosis on Severity of MR 80 patients Preoperative MR was moderate (2) in 78 patients (97.5%) and moderate-severe (3) in 2 patients (2.5%). MR was classified as rheumatic (32%), ischemic (32%), functional (21%), and myxomatous (15%). The etiology of mitral regurgitation before AVR was independently correlated with MR improvement Vanden Eynden F. et al. Ann Thorac Surg 2007;83:1279 84

Natural History and Predictors of Outcome in Patients With Concomitant Functional MR at the Time of AVR AS patients with FMR 2 and 1 additional risk factor LA >5 cm preoperative pavgradient <60 mm Hg, AF were at increased risk for the composite outcome and of MR>2 at 18 months postoperatively. Ruel M. et al. Circulation. 2006;114[suppl I]:I-541 I-546

LV reverse remodeling imparted by AVR for severe aortic stenosis; is it durable? A cardiovascular MRI study sponsored by the AHA Pre-AVR, the grade of MR was 0 through 2+ (moderate MR). Post-AVR, the MR remained stable or decreased late in 80% and increased in two patients. The favorable changes in LV mass and LV EDVI post-avr were highly correlated with MR improvement. Biederman R, et al. Journal of Cardiothoracic Surgery 2011, 6:53

Aortic valve replacement for aortic stenosis in patients with concomitant mitral regurgitation: should the mitral valve be dealt with? Meta-analysis of 17 studies with 3053 pts Reduction in the trans-mitral pressure gradient Reverse ventricular remodeling as demonstrated by a reduction in LV mass and LVED diameter. Reverse remodeling may play a further role in patients with evidence of LV dilatation, where mitral valve leaflet tethering occurs secondary to outward displacement of the papillary muscles Independent predictors of improvement in MR following AVR Higher preoperative LV mass Larger LVEDD Larger LVEDV Etiology of preoperative MR did not have a significant effect on the improvement of MR postoperatively Harling L. et al. European Journal of Cardio-thoracic Surgery 40 (2011) 1087

Aortic valve replacement for aortic stenosis in patients with concomitant mitral regurgitation: should the mitral valve be dealt with? Meta-analysis of 17 studies with 3053 pts Harling L. et al. European Journal of Cardio-thoracic Surgery 40 (2011) 1087 1096

INDIDENCE AND ETIOLOGY OF MR IN PATIENTS WHO UNDERWENT TAVR

Prevalence of moderate/severe mitral regurgitation in patients undergoing TAVI European Heart Journal (2014) 35, 2627 2638

Etiology of Mitral Regurgitation in Patients Undergoing TAVR MR is usually more frequent than functional MR in the general population, functional MR accounts for approximately 50% of patients with MR in patients who have undergone TAVR. No study to date has reported the incidence of mixed MR etiologies,. J Am Coll Cardiol 2014;63:2643 58

Impact of significant MR on mortality after TAVR European Heart Journal (2016) 37, 2226 2239

Predictors of One-Year Mortality After TAVI for Severe Symptomatic Aortic Stenosis N=1391 Previous MR 2 is an independent predictor of 1-year mortality Zahn R et al. Am J Cardiol 2013;112:272-279

TAVI - Outcomes of Patients With Moderate or Severe MR Degree of MR After TAVR and at 1-Year FU in Patients With Moderate or Severe MR at Baseline Multivariate predictors of Reduced MR at 1-year FU MR reduction may be less likely in patients with structural mitral valve disease (deformed leaflets or moderate or severe annular calcification). Toggweiler S. et al. J Am Coll Cardiol 2012;59:2068 74

Coexisting Mitral Regurgitation Impairs Survival After TAVI Meta-analysis n=13672pts Early all-cause mortality Overall all-cause mortality Ann Thorac Surg 2015;100:2270 7

Meta-Analysis of the Impact of Mitral Regurgitation on Outcomes After TAVI Meta-analysis of 8 studies involving 8,927 patients Residual MR Chakravarty T. et al. Am J Cardiol 2015;115:942-949

Clinical impact and evolution of MR after TAVR a meta-analysis 8 studies including 8015 pts SEV: 3474 pts BEV: 4492 pts Nombela-Franco L, et al. Heart 2015;0:1 11

Changes in Mitral Regurgitation After TAVI J Am Coll Cardiol 2014;63:2643 58

Changes in Mitral Regurgitation After TAVI MR in Patients Referred for TAVI Using the Edwards Sapien Prosthesis Mechanisms and Early Postprocedural Changes N=254 Catheter Cardiovasc Interv 75:43 49 (2010) J Am Soc Echocardiogr 2012;25:160-5

5-year outcomes of TAVI or surgical AVR for high surgical risk patients with aortic stenosis - PARTNER 1 Lancet 2015; 385: 2477 84

Evaluation of Flow After TAVR in Patients With Low-Flow Aortic Stenosis JAMA Cardiol. 2016;1(5):584-592

Mitral and aortic regurgitation following TAVR Heart 2016;102:701 706

Predictive Factors Associated With Improvement in MR Severity After Aortic Valve Replacement (SAVR and TAVR) MR etiology (functional vs. organic) Absence of pulmonary hypertension Absence of AF LVEF (low vs. normal) and LV diameters Mean gradient Residual Aortic regurgitation Increased LA size Coronary artery disease or previous MI Prosthesis patient mismatch SAVR TAVR SAVR TAVR SAVR TAVR SAVR TAVR SAVR TAVR SAVR TAVR SAVR SAVR SAVR Absence of mitral annular calcification with TAVR restriction Valve type (ES vs. CoreValve) TAVR Greater improvement Deeper implantation Core valve with ES TAVR J Am Coll Cardiol 2014;63:2643 58

Mitral Regurgitation After TAVR N=1110, MR 3 16% The presence of calcific burden in moderate to severe degrees within the mitral annulus and leaflets associates with greater stiffness of mitral structures, suggesting an organic nature of mitral valve disease, thus hindering MR improvement after TAVR. If this high degree of calcification appears together with a larger annulus diameter, it may preclude from regression of the dilation despite correction of the ventricular pressure overload. Only 13.1% of patients with persistent MR met criteria for percutaneous mitral repair J Am Coll Cardiol Intv 2016;9:1603 14

Percutaneous treatment of MR after TAVR MitraClip European Heart Journal (2016) 37, 2226 2239

Coronary sinus annuloplasty. The cardiac dimensions CARILLON device Mitralign annular plication Valtech CardioBand European Heart Journal (2016) 37, 2226 2239

Improvement of functional capacity after staged percutaneous treatment in 12 patients with aorto-mitral bivalvular heart disease. 254 patients underwent TAVI. 17 patients (6.7%) had preoperative severe MVR that remained unchanged after TAVI. Due to exacerbation of symptoms 12 patients were subsequently submitted to MV repair with the MitraClipVR device. Staging of the two interventions allows the possibility of a spontaneous regression of the MVR after sole treatment of AVS and may prevent unnecessary potentially dangerous treatments. The percutaneous approach is more amenable for a staged strategy. TAVI does not seem to impact on the technical feasibility and complexity of a subsequent MitraClipVR therapy. Catheterization and Cardiovascular Interventions 82:E552 E563 (2013)

Surgical and interventional management of mitral valve regurgitation: a position statement from the ESC Working Groups on Cardiovascular Surgery and Valvular Heart Disease Eur Heart J. 2015 Jul 7

MANAGEMENT OF CONCOMITANT MODERATE TO SEVERE MR IN PATIENTS WITH SEVERE AS

Decisional Algorithm for Management of Patients With Severe Aortic Stenosis and Concomitant Mitral Regurgitation J Am Coll Cardiol 2014;63:2643 58

TAKE HOME MESSAGES I Significant mitral regurgitation (MR) is a common entity ( 15-20%) in patients with severe aortic stenosis undergoing SAVR or TAVI Preoperative quantification of MR should be performed with the effective regurgitant orifice (EROA). Vena contracta might be used to corroborate the quantitative results. Significant MR seems to have a negative impact on early and late survival in patients undergoing SAVR or TAVI.

TAKE HOME MESSAGES II Moderate severe MR improved in about 50% of the patients following SAVR or TAVI especially in those with LV dysfunction and functional MR The decision-making process should be based in the assessment of operative risk, MR severity, etiology and likelihood of MR improvement after isolated AVR.

THANK YOU