Transcatheter Mitral Valve Repair Should Be the Standard of Care for Functional Mitral

Regurgitation

Michael Mack, MD Baylor Scott & White Health

Dallas, TX

Abbott- Co- PI of COAPT Trial of Abbott Vascular

Medtronic-Study Chair Apollo Trial

Edwards Lifesciences- Co-PI of PARTNER 3

Conflict of Interest Disclosure

FMR Disease of the Left Ventricle NOT the Mitral Valve

Normal LV Dilated LV tethering one or both leaflets

Volume overload Annular-Ventricular dilatation

FMR-Vicious Cycle

?

Transcatheter Mitral Valve Repair MitraClip System

Alfieri “Edge-to-Edge” Repair

COAPT vs MITRA-FR The Tale of Two Trials!

Lower Rate of HF Hospitalization And Mortality at 24 Months

Rate of Death or HF Hospitalization At 1 Year Did Not Differ

Possible Role For The Device

# at Risk: MitraClip + GDMT 302 269 238 219 189 128 93

GDMT alone 312 272 223 185 144 89 68

0

100

200

300

400

0 6 12 18 24 30 36

Cum

ulat

ive

HF

Hos

pita

lizat

ions

(n)

Time after randomization (months)

MitraClip + GDMT GDMT alone

HR [95% CI]# = 0.49 [0.37, 0.63] P=0.00000006

NNT = 3.0 [95% CI 2.4, 4.0]

378 in 196 pts

220 in 114 pts

#Joint frailty model

Primary Effectiveness Endpoint All Hospitalizations for HF within 36 months

All patients, ITT, including crossovers

299 in 158 pts

169 in 95 pts

NNT = 3.2 [95% CI 2.5, 4.5]

COAPT at 3 Years

HR = 1.01 ; 95% CI 0.77 to 1.34

ITT Primary composite endpoint - All-Cause Death - First Unplanned rehospit for HF

Medical treatment

Mitraclip + Med. treat.

2 years

MITRA FR at 2 Years

The Problem

Two trials • Same patient population • Same disease • Same treatment • Same timeframe

Diametrically opposite results

Where Are We And What Do We Do?

Courtesy Joann Lindenfeld

More Patients

Longer Follow-up

Better Medical Therapy

More Severe MR

Less Dilated Left Ventricles

Better Acute Outcomes

More Durable Result

More Disproportionate MR !

14

COAPT vs. MITRA-FR

JACC Cardiovasc Imaging 2019

FMR “Responders”

Disproportionate MR- Grayburn

Tertiary MR- Carabello

Valvular Secondary MR- Garbi and Lancellotti

Severe Functional Mitral Regurgitation Can Take Place in One of Two Ways

MR

LV

LA

Severe and Proportionate MR

P3 P1

A2

MR LV remodeling and dilatation

Severe Functional Mitral Regurgitation Can Take Place in One of Two Ways

MR

LV

LA

MR

LV

LA

Severe and Proportionate MR

Severe and Disproportionate MR

P3 P3 P1 P1

A2 A2

MR LV remodeling and dilatation

LBBB Inferior-posterior MI

EROA is Related to LV End-Diastolic Volume

19

LV End-Diastolic Volume (ml)

0.00

0.10

0.20

0.30

0.40

0.50

0.60

100 150 200 250 300 350

ERO

A (c

m2)

EROA vs LVEDV at LVEF 30%, RF 50%

Peak Vel 6 m/sLVSP 160, LAP 16 mmHg

Peak Vel 5 m/sLVSP 120, LAP 20 mmHg

Peak Vel 4 m/sLVSP 90, LAP 26 mmHg

0.4

0.3

0.2

Grayburn, Carabello, Hung, et al, JACC 2014

Spectrum of Severe Secondary MR

20

MR correction likely to be beneficial

Transplant, LVAD, Hospice

Secondary MR is a Disease of the Left Ventricle

Disproportionately Severe FMR

It is the valve, not the ventricle!

Courtesy Paul Grayburn

Severe Functional Mitral Regurgitation Can Take Place in One of Two Ways

MR

LV

LA

Severe and Proportionate MR

P3 P1

A2

MR LV remodeling and dilatation

Severe Functional Mitral Regurgitation Can Take Place in One of Two Ways

MR

LV

LA

MR

LV

LA

Severe and Proportionate MR

Severe and Disproportionate MR

P3 P3 P1 P1

A2 A2

MR LV remodeling and dilatation

LBBB Inferior-posterior MI

Disproportionately Severe MR Proportionately Severe MR

LVEDV 165 ml Elliptical LV LVEF 35%

LVEDV 305 ml Spherical LV LVEF 30%

EROA 0.3 cm2 RgV 48 ml

EROA 0.3 cm2 RgV 39 ml

Courtesy Paul Grayburn

Proportionate MR will respond to treating the ventricle- GDMT +/- CRT

Disproportionate MR will need treatment of the valve- GDMT alone will fail

Atrial functional MR needs rate/rhythm control but NOT GDMT- needs MR correction of the valve

Proportionate vs. Disproportionate MR

26

0.00

0.10

0.20

0.30

0.40

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0.60

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100 125 150 175 200 225 250 275 300 325 350 375 400

ERO

A (c

m2)

LV End-Diastolic Volume (mL)

LVEF 30% RF 50%

MR Vmax 4 m/s VTI 150 cm

MR Vmax 5 m/s VTI 180 cm

MR Vmax 6 m/s VTI 210 cm

RF ≤ 50% and/or LVEF ≤ 30% LV is dominant lesion

RF ≥ 50% and/or LVEF ≥ 30% MR is dominant lesion

Grayburn, Sannino, Packer JACC Img 2019

Trials of Heart Failure Therapies and FMR

Packer and Grayburn Circulation 2019

COAPT AND MITRA-FR

Analysis of both trials has helped define the

• Responder population • Predictors of success

This wouldn’t have been possible by either trial alone

Pooled analysis of the echo data will help further refine the patients who are most likely to benefit

COAPT Takeaways

Important to achieve optimal MR reduction

MR reduction can be achieved with GDMT/CRT/PCI, so exhaust these options before considering mitral therapy in FMR (COAPT)

Is it the valve or the ventricle? Disproportionately severe FMR (larger EROA, smaller LVEDV) is a more likely group for success

How to Maximize MitraClip Success in FMR

Maximal GDMT pre procedure REALLY,REALLY works

Mod-severe or Severe MR despite GDMT

Complete correction of MR- experienced operators

Durable result

Continuation (or up-titration) of GDMT

The more severe the MR and the less dilated the LV, the better the result

TAVR Heart Team

33

Interventional Cardiologist

Cardiac Surgeon

TMVR Heart Team

34

Patient

Interventional Cardiologist

Imagers

Cardiac Surgeon

Heart Failure

Specialist

COAPT Has This Trial Changed the Management of Functional MR ?

Maybe!

Just FDA approved in US

Needs CMS reimbursement in US

Results of RESHAPE Trial (best 2 of 3?)

•Accurate, evaluable echo imaging will be key to define responder population

Needs proper selection of only those patients likely to benefit • Moderate-severe or severe MR despite optimal GDMT with some preservation of LV function • Disproportionate vs. Proportionate MR

•Heart Failure Specialist Will Become a Key Member of the Heart Team

EROA LVEDV

Transcatheter Mitral Valve Repair Should�Be the Standard of Care for Functional Mitral�Regurgitation����Michael Mack, MD�Baylor Scott & White Health�Dallas, TXSlide Number 2FMR�Disease of the Left Ventricle NOT the Mitral Valve� FMR-Vicious CycleSlide Number 5Slide Number 6Primary Effectiveness Endpoint�All Hospitalizations for HF within 36 months�All patients, ITT, including crossoversSlide Number 8The ProblemSlide Number 10Slide Number 11Slide Number 12Slide Number 13Slide Number 14Slide Number 15FMR “Responders”Slide Number 17Slide Number 18EROA is Related to LV End-Diastolic VolumeSpectrum of Severe Secondary MRSecondary MR is a Disease of the Left VentricleDisproportionately Severe FMRSlide Number 23Slide Number 24Slide Number 25Proportionate vs. Disproportionate MRSlide Number 27Trials of Heart Failure Therapies and FMRCOAPT AND MITRA-FRCOAPT TakeawaysHow to Maximize MitraClip Success in FMRSlide Number 32TAVR Heart TeamTMVR Heart TeamCOAPT�Has This Trial Changed the Management of Functional MR ?