Department of Surgery, University of Pennsylvania Health System

Which Operation is Best for Severe Ischemic MR: Repair or Replace?

Michael AckerWilliam Measey Professor of Surgery

Chief of Division of Cardiovascular SurgeryDirector of Heart and Vascular Center

University of Pennsylvania Health System

AHA/ACC and ESC Guidelines

No conclusive evidence for superiority of

repair or replacement

• Class I Level C evidence for IMR patients undergoing CAB w/ EF > 30%

• Class IIa Level C evidence for IMR patients undergoing CAB w/ EF < 30%

• Class IIb Level C evidence for IMR patients not undergoing CAB

• Class IIb Level C evidence for severe secondary MR

Treatment Choice is Controversial

• Lower periop morbidity and mortality with repair

– Vasileva et al, Eur J Cardiothoracic Surg 2011;39:295-303

• Better long-term correction with replacement

– Di Salvo et al, J Am Coll Cardiol. 2010; 55:271-82– Grossi et al, J Thorac Cardiovasc Surg 2001;122:1107-24– Gillinov et al, J Thorac Cardiovasc Surg 2001;122:1125-41

• Based on retrospective observational studies

• Need randomized evidence

4

Functional MR secondary to dilated cardiomyopathy:

Bolling Hypothesis: “an annular solution for a ventricular problem”-- such that reconstruction of the MV annulus’ geometric abnormality by an undersized ring restores valvular competency, alleviates the excessive ventricular workload, improves ventricular geometry and improves ventricular function.

Department of Surgery, University of Pennsylvania Health System

Mitral Annuloplasty Rings

Reduce posterior annular circumferencePush posterior leaflet forward for better coaptation ie decrease septal lateral dimension

Department of Surgery, University of Pennsylvania Health System

MV Repair Techniques for Functional MR

(Ischemic or Non-ischemic)

Undersized Annuloplasty Ring- standard of care; most common of repair techniques

?Techniques to specifically address leaflet tethering—Promising but not fully tested:

cutting secondary chordspapillary muscle relocation

Department of Surgery, University of Pennsylvania Health System

Downsized, rigid rings showed positive results at 4-year follow-up

Methods: 85 consecutive patients with previous infarction, LV dysfunction (EF 30%) and severe MR underwent CABG and restrictive mitral annuloplasty with stringent downsizing (2 rigid complete ring sizes).

Pre-op 4 years p-value

NYHA class 2.9 1.2 <0.0001

LVEDD (mm)

59.8 54.2 <0.0001

LVESD (mm) 46.3 39.3 <0.0001

LA dimension (mm)

45 42 <0.01

MR grade 3.0 0.8 <0.0001LVEDD = left ventricle end-diastole dimension; LVESD = left ventricle end-systolic dimension; LA = left atrium

Bax et al. Restrictive annuloplasty and coronary revascularization in IMR results in reverse left ventricular remodeling. Circ 110:II 103-II108 2004Braun et al: Preoperative left ventricular dimensions predict reverse remodeling following restrictive mitral annuloplasty in IMR. Eur J CT Surg 27(5):847-853

• 8% mortality• No recurrence of > 2 MR at 18 mo• No reverse remodeling seen • with LVEDD>65mm

Cannot Discount effect of RevascularizationOn Hybernating Myocardium leading to Reverse Remodeling

Tethering Mechanism for recurrent MR after repair

Tethered Leaflets

Tethered Leaflets

Severe IMR Randomized Comparison of MV Repair vs Replacement Moderate/severe MR by TTE assessment insurviving pts at 30 days, 6, 12 and 24 months

Severe IMR Randomized Comparison of MV Repair vs Replacement Cumulative incidence of MR recurrence and/or death over 2 years (n=116)

11

• Preservation of entire MV apparatus has been demonstrated to preserve ventricular geometry, decrease wall stress, improve systolic and diastolic function

• Must maintain chordal, annular and subvalvular continuity

Is the Best Repair a Replacement?

Comparisons of results to Era where subchordal apparatus was excised not valid

(Enriquez-Sarano et al. Circulation 2003;108:253-256)

MV Repair vs Replacement

May

Mayo Clinic: ICM -- no difference in survival between replacement and repair

13

Mitral valve repair or replacement for ischemic mitral regurgitation? The Italian Study on the Treatment of Ischemic Mitral Regurgitation (ISTIMIR) Lorusso R et al. J Thorac Cardiovasc Surg 2013; 145:129-39

Propensity matched

14

Mitral valve repair or replacement for ischemic mitral regurgitation? The Italian Study on the Treatment of Ischemic Mitral Regurgitation (ISTIMIR) Lorusso R et al. J Thorac Cardiovasc Surg 2013; 145:129-39

Primary Endpoint

• Degree of left ventricular reverse remodeling − Assessed by left ventricular end systolic volume

index (LVESVI) using TTE at 12 months− Group difference based on Wilcoxon Rank-Sum

test with deaths categorized as lowest LVESVI rank

• Powered (90%) to detect an improvement of 15mL/m2 from repair to replacement in LVESVI at 12 months

Median change in LVESVI Ch

ange

in LV

ESVI

(mm

/m2 )

Repair Replacement Repair Replacement (All pts) (All pts) (Survivors) (Survivors)

Median with 95% CI for change in LVESVI from baseline to 1 yr

Z=1.33, p=0.18 (All pts)

Recurrent MR at 1 year

Repair Replacement0

5

10

15

20

25

30

35 32.6

2.3

Moderate or Severe Recurrent MR

Perc

ent w

ith m

oder

ate

or s

ever

e re

-cu

rren

t MR p < 0.001

LVESVI with Recurrent MR

Mean LVESVI at 12 Months for Patients with Recurrent MR

Repair with MR Repair without MR0

10

20

30

40

50

60

70

Mean LVESVI for Patients Undergoing Repair

Baseline12 Months

Mea

n LV

ESVI

p < 0.001

Primary end point

LVESVI (ml/m2) MR ≥2+ (%)

RIME Trial

CABG 67.4 (-6%) 50

CABG + MV repair 56.2 (-28%) 4

P-value 0.002 <0.001

CTSN Mod MR Trial

CABG 46.1 (-17%) 30

CABG + MV repair 49.6 (-16%) 11

P-value NS <0.001

CTSN Severe MR Trial

CABG + MV repair (overall) 54.6 (-11%) 33

CABG + MV repair (recurrent MR) 64.1 (+5%) 100

CABG + MV repair (no recurrent MR) 47.3 (-22%) 0

CABG + MV replacement 60.7 (-10%) 2

Comparison with other randomised controlled trials

Mortality

30 Day Mortality: 1.6% (repair) vs. 4.0% (replacement), p =0.26

12 Month Mortality: 14.2% (repair) vs. 17.6% (replacement), p =0.47

MACCE at 12 Months

Serious Adverse Events

Heart Failu

re

Stroke

MV Re-operation

Bleeding

Loca

lized In

fection

Re-Hosp

italiza

tions0

20

40

60

80

100

120

Repair Replacement

Rate

(100

/pt-

yrs)

Overall SAE Rate (100-pt years)202.1 (repair) vs. 189.0 (replacement) p=0.49

P=NS

P=NSP=NS

P=NS

P=NS

P=NS

Quality of Life at 1 year

Repair Replacement Repair Replacement0

5

10

15

20

25

30

35

40

45

50

SF-12

Mea

n Sc

ore

MLHFSF-12

Δ=16.6% Δ=18.4%

Δ=46.9%

Δ=19.6%

NYHA Classification & Death

Restrictive mitral valve annuloplasty versus mitral valve replacement for functional ischemic mitral regurgitation: Am exercise echocardiographic study. Fino et al. J Thorac Cardiovasc Surg 2014;148:447-53

26 Physio-17%28 Physio-51%30 Physio-29%32 Physio-3%

27 CE-23%29 CE-26%31 CE-3%27 SJ-8%29 SJ-26%25 SJ-3%27 Carbomedics-8%29 Carbomedics-3%

MV Repair-35MVR - 35

Restrictive mitral valve annuloplasty versus mitral valve replacement for functional ischemic mitral regurgitation: Am exercise echocardiographic study. Fino et al. J Thorac Cardiovasc Surg 2014;148:447-53

Determinants of long term functional capacity in patients undergoing mitral valve annuloplasty or mitral valve replacement for ischemic mitral regurgitation.

Fino et al. AHA Nov 2014

10 Variable Model of MR Recurrence and/or Death

AgeBMIGenderRaceEROA Basal AneurysmNYHAHistory of CABGHistory of PCI History of Ventricular Arrhythmia

ROC Curve: 10 Variable model of Recurrence/Death

Basal Aneurysm

Preoperative 3D Valve AnalysisPredicts Recurrent IMR after Mitral Annuloplasty—Gorman lab

Predictors of IMR recurrence by univariate and multivariate logistic regression analysis

Univariate analysis Multivariate analysis

Variable OR 95% CI P Value OR 95% CI P Value

Septolateral dimension, mm 1.00 (0.86-1.17) 0.975 - - -

Commissural width, mm 0.98 (0.88-1.10) 0.772 - - -

Mitral transverse diameter, mm 0.97 (0.84-1.12) 0.688 - - -

Mitral annular area, mm2 1.00 (1.00-1.00) 0.781 - - -

Annular circumference, mm 1.01 (0.96-1.06) 0.846 - - -

Mitral valve tethering volume, mm3 1.00 (1.00-1.00) 0.069 - - -

Mitral valve tethering index 2.48 (1.19-5.17) 0.015 - - -Segmental tethering angle, °

A1 1.09 (1.00-1.19) 0.058 - - -

A2 1.05 (0.99-1.12) 0.094 - - -

A3 1.10 (1.02-1.19) 0.019 - - -

P1 1.07 (0.99-1.16) 0.076 - - -

P2 1.13 (1.04-1.22) 0.005 - - -

P3 1.28 (1.11-1.49) 0.001 1.28 (1.11-1.49) 0.001

50 pts with Severe IMR undergoing MV repair with small annuloplasty ringcomparing recurrence of mod to severe MR to those without recurrence

Conclusions

-2D echocardiographic studies identified different predictors of IMR recurrence,

but results are inconsistent and generally inadequate to predict IMR recurrence

-3D echocardiography combined with valve modeling is predictive of recurrent

IMR

-Preoperative regional leaflet tethering of P3 is a strong independent predictor of

IMR recurrence after undersized ring annuloplasty

-In patients with IMR and a preoperative P3 tethering angle ≥29.9° chordal-

sparing mitral valve replacement rather than mitral valve repair should be

strongly considered

Repair vs Replacement for Severe Ischemic MR

• Does it result in improved survival?– Early/late?--NO

• Does it result in decreased complications?– NO (at one year)

• Does it result in more LV reverse remodeling?– NO (at one year)

• Does it result in improved freedom from hospitalizations or symptoms of heart failure?– NO (at one year)

• Is Replacement a more reliable operation for longterm freedom from recurrent MR?- YES (longterm benefits will be seen because of absence of MR ?)

- Can we predict recurrence?- Predictive models of recurrence of IMR are being developed to allow for customization

of repair vs replacement for individual pt with severe IMR

Conclusions

• Recurrent MR at least to a moderate degree occurs early (6mo) and is a common event at 2 years after MV repair with an undersized annuloplasty ring—clinical impact yet unkown?

• MVR provides a more durable correction of severe IMR with no differences seen in reversal of LV remodeling or clinical outcomes – MR recurrence may have an important effect on long-term outcomes

• MVR with complete chordal sparing is a safe and acceptable option in pts with severe IMR-supported by LEVEL of EVIDENCE “A”

So What Do I Do?

• I continue to repair about 70% of IMR with small complete annuloplasy ring while replacing about 30%– Degree of tethering; age of pt; need for

anticoagulation; – Await 2 and 5 year data on effect of recurrent

moderate MR on clinical outcome• 2 year follow-up to be presented AHA Nov 2015