Clinical Pearls:
Takeaway Points for Aortic
Stenosis and Mitral
Regurgitation Management
in 2014
Hemal Gada, MD, MBA
Assistant Professor of Medicine
Rutgers Robert Wood Johnson Medical School
A Hot 20 Minutes
Aortic Stenosis
Indications for valve replacement are expanding
Access requirements for TF TAVR are getting smaller
Multiple TAVR devices mean more options and better patient care
Mitral Regurgitation
Degenerative (primary) mitral regurgitation needs early surgical referral
Repair vs replace for medically-optimized symptomatic ischemic mitral regurgitation will be driven by surgeon expertise
Percutaneous mitral valve repair indications will continue to evolve and expand into the realm of functional mitral regurgitation
INDICATIONS FOR
AORTIC VALVE
REPLACEMENT ARE
EXPANDING
ACC/AHA Valve Guidelines
Surgery for AS
Asymptomatic(Stage C)
Vmax ≥ 4.0 m/sec-OR-
MG ≥ 40 mmHg
LVEF < 50%(Stage C2)
AVR (I)
Symptomatic(Stage D1)
Other Cardiac Surgery
Vmax ≥ 5 m/sec-OR-
MG ≥ 60 mmHgLow surgical risk
(Stage C1)
Abnormal ETTΔVmax > 0.3 m/sec/y
Low surgical risk(Stage C1)
AVR (IIa)
AVR (IIb)
Nishimura RA et al. J Am Coll Cardiol 2014;63:e57–185
ACC/AHA Valve Guidelines
TAVR for AS
COR LOE
For patients in whom TAVR or high-risk
surgical AVR is being considered, members
of a Heart Valve Team should collaborate to
provide optimal patient care
I C
TAVR is recommended in patients who meet
an indication for AVR for AS who have a
prohibitive surgical risk and a predicted
post-TAVR survival > 12 mos
I B
TAVR is a reasonable alternative to surgical
AVR in patients who meet an indication for
AVR and who have high surgical riskIIa B
Percutaneous aortic balloon dilation may
be considered as a bridge to surgical or
transcatheter AVR in severely symptomatic
patients with severe AS
IIb CNishimura RA et al. J Am Coll Cardiol 2014;63:e57–185
Patient
Surgeon
Cardiologist
Imaging
SpecialistAnesthesia
Consultants
Heart Valve Team
• Cath lab/OR staff
• Nurses, NPs, PAs
• Research staff
• Social work, PT
• Geriatricians
• Coordinators
• Hospital
administrators
• Valve clinic
• Case selection
• Multi-modality imaging
(access site, valve size)
• TAVR procedure
(cath lab/OR)
• Post-op care and FU
All-Cause Mortality (ITT) Crossover Patients Censored at Crossover
71.8%
93.6%
All
-Cau
se M
ort
ality
(%
)
Months
HR [95% CI] = 0.50 [0.39, 0.65]
p (log rank) < 0.0001
Standard Rx (n = 179)
TAVR (n = 179)
30.7%
50.8%
43.0%
68.0%
64.1%
87.5%
53.9%
80.9%
* In an age and gender matched US population without comorbidities,
the mortality at 5 years is 40.5%.
Kapadia S. TCT 2014
Evolution in Patient Selection
in U.S. TAVR Clinical Trials
11.2% 11.0%10.3% 10.3%
9.0%
7.0%
11.8%10.9%
7.3%
5.0%
0%
2%
4%
6%
8%
10%
12%
14%
PARTNER BTAVR
PARTNERIIB
SAPIEN
PARTNERIIB
SAPIEN XT
CoreValveER
Iliofemoral
CoreValveER
ContinuedAccess
TVTRegistry
SAPIEN TF
PARTNER ATAVR
PARTNERTF
ContinuedAccess
CoreValveHR
TVTRegistry
SAPIEN TF
STS
Sco
re
Inoperable (extreme risk) High-Risk
Frailty Assessment
Frailty
Characteristic
Cardiovascular
Health Study –
Fried Measure
PARTNER
Measure
Shrinking: Weight
loss, sarcopenia
Self-report 10lb
weight loss
Albumin less
than 3.5 g/dL
Weakness Grip strength:
lowest 20% (by
gender, BMI)
Same
Poor endurance:
Slowness
Exhaustion
Walking time/15
feet: slowest 20%
(by gender, height)
“Exhaustion” report
Same
Symptomatic AS
Low activity Kcal/week: by
activity
Katz ADL
impairment
Positive for frailty
phenotype
3 or more criteria
present
Same
P. Green, TVT 2012 Courtesy of J. Popma
The Role for TAVR
Operable AS patients
TAVR in 2014
Low
Risk
Surgery (AVR)
irresponsible,
reckless
~65%
Intermed
Risk
¿
“equipoise”
~25%
High
Risk
TAVRor
AVR
OK
~10%
Futile
No
Too
Sick
TAVR
Extr
Risk*
Current TAVR
Clinical Use
* Extreme risk = “inoperable”
ACC/AHA Valve Guidelines
Surgery for AS
Asymptomatic(Stage B)
Vmax 3 m/sec-3.9 m/sec-OR-
MG 20-39 mmHg
LVEF < 50%
Symptomatic
DSE with AVA ≤ 1 cm2
and Vmax ≥ 4 m/sec(Stage D2)
Other cardiac surgery
AVR (IIa)
Nishimura RA et al. J Am Coll Cardiol 2014;63:e57–185
Ye
s
No
AVA ≤ 1 cm2 and LVEF ≥ 50% (Stage D3*)
AS likely cause of symptoms
Paradoxical Low-Flow
Low-Gradient AS
AVR is reasonable in symptomatic patients with
LVEF ≥ 50%
Calcified aortic valve with significantly reduced
leaflet motion
Vmax < 4 m/sec or MG < 40 mmHg
AVA ≤ 1.0 cm2
Provided that:
Stroke volume index < 35 mL/m2
Indexed AVA ≤ 0.6 cm2/m2
Treatment Comparison inNormal EF (NEF), Low-flow (LF), Low-gradient (LG) AS
0%
10%
20%
30%
40%
50%
60%
80%
90%
60 120 180 240 300 360 420 480 540 600 660 720
70%
2-Y
ea
r D
ea
th (
%)
39.7%
41.1%
56.5%
76.9%
0
log rank p= 0.003
Numbers at Risk
A – TAVR 43 39 38 34 34 33 29 26 22A – Surgery 44 33 30 30 28 27 27 26 23B – TAVR 23 21 19 17 15 13 11 10 10B – Std Rx 29 22 15 10 9 9 6 5 4
LF NEF LG – A - TAVR
LF NEF LG – A - Surgery
LF NEF LG – B - TAVR
LF NEF LG – B - Std Rx
Days
Herrmann HC et al. Circulation 2013;127:2316–26
ACCESS
REQUIREMENTS
FOR TF TAVR ARE
GETTING SMALLER
Larger Sheath Size Can Contribute to
Major Vascular Complications
A Sheath to Femoral Artery Ratio (SFAR) ≥ 1.05 is a Predictor of both
VARC Major Vascular Complications and 30-Day Mortality
Sapien or Sapien XT (n = 102)CoreValve (n = 28)
100
80
60
40
20
00.7 0.8 0.9 1.0 1.1 1.2
1.05
Sensitivity
Specificity
(%)
Hayashida K et al. J Am Coll Cardiol CV Int 2011;4:851-8
Vascular Complications/Bleeding:
PARTNER 2B Sheath Size
Comparison
ValveValve
Size
Sheath
ID
Sheath
OD
Minimum
Vessel
Diameter
SAPIEN THV 23mm 22F25F
(8.4mm)7.0mm
SAPIEN XT THV 23mm 18F22F
(7.2mm)6.0mm
SAPIEN THV 26mm 24F28F
(9.2mm)8.0mm
SAPIEN XT THV 26mm 19F23F
(7.5mm)6.5mm
33% reduction in CSA
Leon M. ACC 2013
Events
SAPIEN
(n=271)
SAPIEN XT
(n=282)
n % n % p-value
Vascular:
Major 42 15.5 27 9.6 0.04
Minor 20 7.4 14 5.0 0.23
Bleeding:
Disabling 34 12.6 22 7.8 0.06
Major 44 16.4 44 15.7 0.84
Patients with transfusions 80 29.5 73 25.9 0.40
Vascular
Complications/Bleeding:
PARTNER 2B – at 30 days (AT)
Leon M. ACC 2013
Edwards eSheath
The Edwards expandable sheath (1) features a fold that
expands as the NovaFlex catheter moves through (2,3).
Toggweiler S et al. J Am Coll Cardiol CV Int 2013;6:643-53
Edwards eSheath
14F 16F 18F 20F
Valve SAPIEN 3
26 mm
SAPIEN XT
23 mm
SAPIEN XT
26 mm
SAPIEN XT
29 mm
Sheath ID Unexpanded 4.7 mm 5.3 mm 6.0 mm 6.7 mm
Sheath OD
Unexpanded 6.0 mm 6.7 mm 7.2 mm 8.0 mm
Expanded w/valve 8.0 mm 8.9 mm 8.9 mm 9.9 mm
Rec Minimum Diameter 5.5 mm 6.0 mm 6.5 mm 7.0 mm
SFAR
Unexpanded 1.0 1.12 1.11 1.14
Expanded w/ valve 1.45 1.48 1.37 1.41
Binder RK et al. J Am Coll Cardiol CV Int 2013;3:293-300
Terumo SoloPath
Dimitriadis Z et al. J Am Coll Cardiol CV Int 2013;26:84-9
Terumo SoloPath
Re-collapsible
Sheath Size (Based
on Expanded ID)
19Fr
22Fr
24Fr
Insertion Profile OD
13.5Fr
15Fr
15Fr
23Fr
26Fr
28.5Fr
Features
• 5.3Fr tip diameter
• 25 or 35 cm
working length
• 20 or 30 cm
expandable length
• ~30% reduction in
profile once re-
collapsed
Increasing TF Options for
the Future
SFAR <= 1.05 1.05<SFAR<=1.2 SFAR>1.2
Vessel Diameter in mm 5.0 6.00 6.25 6.50 6.75 7.00 7.25 7.50 7.75 8.00
18 Fr Sheath1.5 1.2 1.2 1.1 1.1 1.0 1 1.0 0.9 0.9
14 Fr Sheath1.2 1 1.0 0.9 0.9 0.9 0.8 0.8 0.8 0.8
13 Fr Sheath1.1 0.9 0.9 0.9 0.8 0.8 0.8 0.7 0.7 0.7
Babaliaros V. TVT 2013
MULTIPLE TAVR
DEVICES MEAN
MORE OPTIONS
AND BETTER
PATIENT CARE
Edwards Lifesciences Medtronic CoreValve
Current Generation Devices
The Great TAVR Device Debate
>100,000 patients treated thru 2014
in >750 interventional centers
around the world!
>95% of TAVR patients have been
treated with either of these
two (very different) devices!
The Great TAVR Device Debate
What’s important?
Differences in major clinical outcomes (definitely death and stroke; possibly PVR, bleeding, and vascular complications)
Differences in softer secondary clinical endpoints (e.g. conduction disturbances)
Preferences based upon specific anatomic situations (e.g. horizontal Ao, high rupture risk), technical device differences, and operator ease-of-use issues
I use it because I know it well, I like it, and I get good outcomes!
No Differences in Mortality at 1 Year
in High Risk and Inoperable Patients
TV
T R
eg
istr
y
FR
AN
CE
2
SO
UR
CE
XT
SO
UR
CE
Co
h2
SO
UR
CE
Co
h1
AD
VA
NC
E
UK
Ita
lia
n
CV
Ex
trem
e R
isk
PR
AG
MA
TIC
CV
Hig
h R
isk
PA
RT
NE
R 1
A
PA
RT
NE
R 2
B
PR
EV
AIL
TA
PR
EV
AIL
EU
PA
RT
NE
R 1
B
PR
EV
AIL
JA
PA
N
26.2, 7710
24.0, 2107
19.5, 2688
23.0, 126924.3, 1038
20.6, 410
12.3, 204
24.2, 348
22.5, 284
23.0, 218
20.5, 214
30.7, 179
14.7, 64
23.7, 104317.9, 996
21.7, 452
15.0, 663
24.3, 489
16.2, 20414.2, 390
0
5
10
15
20
25
30
35
40
SAPIEN Family CoreValve
Mo
rtali
ty (
%)
Rate, Number of Patients
Leon M. TVT 2014
TV
T R
eg
istr
y
SO
UR
CE
XT
SO
UR
CE
Co
h2
SO
UR
CE
Co
h1
AD
VA
NC
E
UK
Ita
lia
n-T
A
CV
Ex
trem
e R
isk
PR
AG
MA
TIC
CV
Hig
h R
isk
PA
RT
NE
R1
A
PA
RT
NE
R 2
B
PR
EV
AIL
EU
AD
VA
NC
E I
I
Ita
lia
n
PA
RT
NE
R 1
B
PR
EV
AIL
TA
S3
TF
PR
EV
AIL
JA
PA
N
Str
oke
* (%
)
Rate, Number of Patients
2.8, 3528
3.6, 2688
2.8, 1269
2.7, 1038
4.1, 870
3.0, 504
1.0, 204
4.7, 348
4.3, 284
3.9, 214
6.7, 179
1.9, 218
1.0, 96
1.6, 643.0, 996
4.0, 489
2.9, 204
4.9, 390
2.1, 194
2.8, 181
0
2
4
6
8
10
SAPIEN Family CoreValve
No Differences in All Strokes at 30 days
in High Risk and Inoperable Patients
*Rate of All Stroke or Major Stroke + Minor Stroke
Leon M. TVT 2014
Dissimilarities in clinical outcomes after TAVR using SAPIEN XT or
CoreValve in different annular zones*
* Favorable aortic annulus zones were defined as those that may enable 5-20% area
oversizing or 2.5-9.5% perimeter oversizing in SAPIEN XT procedures and 20-35% area
oversizing or 9.5-16.2% perimeter oversizing in CoreValve procedures.
Individualized Device Approach in
TAVR: SAPIEN XT or CoreValve
Dvir D, et al. TVT 2014
250 300 350 400 450 500 550 600 650
SAPIEN XT zone
CoreValve zone
26
1.8
29
9.2
30
7.8
34
6.2
39
3.3
39
5.7
44
2.4
48
9.3
50
5.6
55
0.4
55
9.1
CoreValve
23 mm
SAPIEN XT
23 mmSAPIEN XT
26 mm
SAPIEN XT
29 mm
CoreValve
26 mm
CoreValve
29 mm
CoreValve
31 mm
SAPIEN XT
20 mm
Aortic Valve Annulus Area (mm2)
Dvir D, et al. TVT 2014
DEGENERATIVE
MITRAL
REGURGITATION
NEEDS EARLY
SURGICAL
REFERRAL
ACC/AHA 2014 Valve Guidelines
Treatment of MR
First decision
Nishimura RA et al. J Am Coll Cardiol 2014;63:e57–185
Mitral Regurgitation
PrimaryMR
SecondaryMR
ACC/AHA 2014 Valve Guidelines
Primary vs. Secondary MR
Definition of Severe MR
Primary MR Secondary MR
EROA ≥0.4 cm2 ≥0.2 cm2*
Regurgitant volume ≥60 ml ≥30 ml
Regurgitant fraction ≥50% ≥50%
Vena contracta ≥0.7 cm -
Jet areaCentral jet >40% LA or
holosystolic eccentric jet-
* Measurement of the proximal isovelocity surface area by 2D TTE in secondary MR
underestimates the true ERO due to the crescentic shape of the proximal convergence
Nishimura RA et al. J Am Coll Cardiol 2014;63:e57–185
ACC/AHA 2014 Valve Guidelines
Surgery for Primary MR
Nishimura RA et al. J Am Coll Cardiol 2014;63:e57–185
Progressive MR(stage B)
Vena contracta <0.7 cmR Vol <60 mL
RF <50%ERO <0.4 cm2
Primary MR
YES NO
Asymptomatic(stage C)
MV Surgery(llb)
MV Surgery(l)
MV Repair(lla)
Periodic Monitoring
NO YES
Likelihood of successfulRepair >95% and
Expected mortality <1%
LVEF >30%LVEF 30% to ≤60%or LVESD ≥40 mm
(stage C2)
LVEF >60% andLVESD <40 mm
(stage C1)
New onset AF orPASP >50 mm Hg
(stage C1)
Symptomatic(stage D)
Severe MRVena contracta ≥0.7 cm
R Vol <60 mLRF ≥50%
ERO ≥0.4 cm2
LV dilation
Surgery in Asymptomatic Severe
Chronic Primary MR
• MIDA registry (6 international centers) between 1980 and 2004
• 1,021 asymptomatic pts with flail leaflets causing severe MR with LVEF>60% and LVESD<40
mm
• MV surgery w/i 3 mos (median 14 d; 93% repair; 22% concomitant CABG) vs. med Rx (with MV
surgery in 59% at median of 1.65 years, 87% repair); 10 yr median FU
• Outcomes in 324 propensity matched pairs were compared
Suri et al. JAMA. 2013;310:609-16
HR [95%CI] =
0.52 [0.35-0.79]
P=0.002
HR [95%CI] =
0.44 [0.26-0.76]
P=0.003
Survival CHF
11%
24%
53%
60%
Su
rviv
al (%
)
100
80
60
40
20
0
Follow-up (years)
0 5 10 15 20
Medical management
Early surgery
324
324
276
295
157
160
53
35
8
10
Ris
k o
f C
HF
(%
)
50
40
30
20
10
0
Follow-up (years)
0 5 10 15 20
Medical management
Early surgery
324
324
253
289
142
149
48
31
3
9
HR (95%CI) =
0.51 (0.24-1.08)
P=0.08
HR (95%CI) =
0.22 (0.08-0.56)
P=0.002
HR (95%CI) =
0.11 (0.01-0.84)
P=0.03
MA
CE
(%
)
Ca
rdia
c M
ort
ality
(%
)
All
-ca
us
e M
ort
ality
(%
)
Time after Baseline, yearsNo. at risk
CONV
OP
50
40
30
20
10
0
0 2 4 6 8 10 12
207
207
199
203
174
179
138
137
108
94
58
00
38
32
Time after Baseline, yearsNo. at risk
CONV
OP
50
40
30
20
10
0
0 2 4 6 8 10 12
207
207
199
203
174
179
138
137
108
94
58
00
36
32
Conservative
MV surgery
Time after Baseline, yearsNo. at risk
CONV
OP
50
40
30
20
10
0
0 2 4 6 8 10 12
207
207
199
202
172
170
136
134
108
93
54
00
31
31
19%
1%
6%6%
15%
4%
Conservative
MV surgery
Conservative
MV surgery
Kang et al. J Am Coll Cardiol. 2014;63:2398-407
Surgery in Asymptomatic Severe
Chronic Primary MR
• 2 S. Korean centers from 1996-2009
• 610 asymptomatic pts ≤85 yo with severe MR (ERO ≥0.4 cm2) with LVEF>60%, LVESD<40 mm
• Treated with MV surgery w/i 6 mos (94% repair; 10% concomitant CABG) vs. med Rx (with
censoring when indications for surgery developed)
• Outcomes in 207 propensity matched pairs were compared (median 8 yr FU)
MACE = cardiac death, repeat MV surgery, and HF hospitalization
FDA MitraClip Approval
October 24, 2013
The MitraClip is approved
for treatment of patients with
3+-4+ primary (degenerative) MR
(DMR) who are at “prohibitive risk” for
mitral valve surgery and are likely to
benefit from MR reduction
MitraClip in Prohibitive-risk
DMR
Relationship between Discharge MR Grade
and 1-year HF Hospitalizations*
Lim SD et al. J Am Coll Cardiol 2014;64:182–92
* with death
counted as a HF
hospitalization
28%
increase
HF
Ho
sp
italizati
on
Rate
per
Pati
en
t-Y
ear
1.0
0.8
0.6
0.4
0.2
0.0
0.50
MR ≤1+
N=65
0.35
MR = 2+N=35
MR = 3+-4+N=18
0.97
0.68
0.87
0.39
60%
reduction
30%
reduction
Su
rviv
al
1.0
0.9
0.8
0.3
0.2
0.1
0.7
0.6
0.5
0.4
0.0
0 40 80 120 160 200 240 280 320 360 400
83.3%80.0%
52.4%
Survival at
1 year
MR severity
at discharge: Survival at 1 year (unadjusted):
≤1+ (n=66)
2+ (n=35)
3+/4+(n=22)
p=0.61 for ≤1 vs 2+ at discharge
p=0.001 for ≤1 vs 3+/4+ at discharge
p=0.02 for 2+ vs 3+/4+ at discharge
MitraClip in Prohibitive-risk
DMR
• 127 pts from EVEREST studies• Mean age 82 yrs, 87% NYHA III/IV, mean STS score 13.2%. MitraClip success 95.3%• 1-year survival 75.2%; survival according to d/c MR:
Days
Lim SD et al. J Am Coll Cardiol 2014;64:182–92
ACC/AHA 2014 Valve Guidelines
TMVR for DMR
COR LOE
Transcatheter MV repair may be
considered for severely
symptomatic pts (NYHA class
III/IV) with chronic severe primary
MR (stage D) who have a
reasonable life expectancy but a
prohibitive surgical risk because
of severe comorbidities
Nishimura RA et al. J Am Coll Cardiol 2014;63:e57–185
REPAIR VS REPLACE
FOR MEDICALLY-
OPTIMIZED
SYMPTOMATIC
ISCHEMIC MR WILL BE
DRIVEN BY SURGEON
EXPERTISE
Secondary MR
CAD RxHF Rx
Consider CRT
Symptomatic severe MR (Stage D)
Asymptomatic severe MR (Stage C)
Progressive MR (Stage B)
Persistent NYHA Class III-IV symptoms
MV Surgery (IIb)
Nishimura RA et al. J Am Coll Cardiol 2014;63:e57–185
ACC/AHA 2014 Valve Guidelines
Surgery for Secondary MR
Periodic Monitoring
Medical treatment
PCI
CABG only
CABG + MVr/R
Is MV Surgery Beneficial in
FMR?• 4,989 pts with CAD and mod/sev ischemic MR at Duke between 1990-2009 • Treated with MED only (1,800; 36%), PCI only (1,295; 26%), CABG only (1,651; 33%) and
CABG + MV repair or replacement (243; 5%) • Propensity adjusted multivariable outcomes at median FU 5.4 yrs:
PCI vs Med: Adj HR (95%CI) = 0.83 (0.76 - 0.92), P=0.0002
CABG vs. Med: Adj HR (95%CI) = 0.56 (0.52 - 0.62), P<0.0001
CABG+MVRR vs. Med: Adj HR (95%CI) = 0.69 (0.57 - 0.82), P<0.0001
P for interaction for MR severity = 0.61
Median adj
survival
5.6 years
6.8 years
9.7 years
8.1 years
Su
rviv
al
1.0
0.9
0.8
0.3
0.2
0.1
0.7
0.6
0.5
0.4
0.0
No. at risk0
Medical treatmentPCICABG onlyCABG + MVRR
180012951651243
1 2
119810381402181
3 4
8778581160144
5 6
633677901103
7 8
46148667372
9 10
33235240248
Castleberry AW et al. Circulation 2014;129:2547-56
Meta-analysis of Repair vs.
Replacement for Ischemic MR
12 non-randomized studies, 2,508 pts, 64% repair, 36%
replacement
Random effects meta-analysis:Repair vs. replacement
Endpoint (n studies) HR (or OR) [95%CI] P value
Hospital death (11) 0.56 [0.38, 0.85] 0.006
- Studies after 1988 (7) 0.70 [0.44, 1.12] 0.14
Long-term death (11) 0.86 [0.66, 1.13] 0.28
- Propensity adjusted (4) 1.05 [0.92, 1.19] 0.46
Recurrent MR ≥2+ (5) 7.51 [3.70, 15.23] <0.0001
Reoperation (4) 1.49 [0.91, 2.46] 0.16
Dayan V et al. Ann Thorac Surg 2014;97:758–66
Severe MR (SMR) Trial Design
• 251 pts with severe ischemic FMR
• Randomized to MV repair with complete rings vs. chordal-sparing MV replacement
• Mean EROA ~0.40 cm2; 86% concomitant procedures (75% CABG, TV repair, Maze)
En
rollm
en
t
Excluded (n=3207)
• Did not meet inclusion criteria (n=3011)
• Refused to participate (n=131)
• Other (n=65)
All
oc
ati
on
An
aly
sis
Fo
llo
w-u
p
Allocated to Mitral Valve Repair (n=126)
• Received MV Repair (n=115)
• Received MV Replacement (n=11)
Assessed for Eligibility
(n=3458)
Allocated to Mitral Valve Replacement (n=125)
• Received MV Replacement (n=124)
• Received MV Repair (n=1)
Randomized
(n=251)
• Withdrawal before month 12 (n=3)
• Death before month 12 (n=18)
• Withdrawal before month 12 (n=1)
• Death before month 12 (n=22)
Primary Endpoint Analysis (n=126)
Excluded from Analysis (n=0)
Primary Endpoint Analysis (n=125)
Excluded from Analysis (n=0)
2 year FU planned
Acker MA et al. NEJM 2013;45:381-387
SMR Trial: 1° Endpoint
• 251 pts with severe ischemic FMR
• Randomized to MV repair with complete rings vs. chordal-sparing MV replacement
• Mean EROA ~0.40 cm2; 86% concomitant procedures (75% CABG, TV repair, Maze)
Acker MA et al. NEJM 2013;45:381-387
1 EP = Median Change in LVESVI from baseline to 1 year
P=0.18
Med
ian
Ch
an
ge in
LV
ES
VI
(mm
/m2)
Repair
(All pts)
Replacement
(All pts)
Repair
(Survivors)
Replacement
(Survivors)
10.0
7.5
5.0
2.5
0.0
-2.5
-5.0
SMR Trial: Recurrent MR
• 251 pts with severe ischemic FMR
• Randomized to MV repair with complete rings vs. chordal-sparing MV replacement
• Mean EROA ~0.40 cm2; 86% concomitant procedures (75% CABG, TV repair, Maze)
Acker MA et al. NEJM 2013;45:381-387
Recurrent MR at 1 year
28.4 2.3
4.2
2.3%
0
10
20
30
40
Repair (n=126) Replacement (n=125)
Rec
urr
en
t M
R (
%) Severe
Moderate
32.6%
There were no
significant 1-year
differences in:
• LVESVI
• NYHA
• SF-36 scores
• MLwHF scores
• MV reoperation
• Death
• MACE
P<0.001
SMR Trial: Impact of Recurrent MR
• 251 pts with severe ischemic FMR
• Randomized to MV repair with complete rings vs. chordal-sparing MV replacement
• Mean EROA ~0.40 cm2; 86% concomitant procedures (75% CABG, TV repair, Maze)
Acker MA et al. NEJM 2013;45:381-387
Mean Change in LVESVI
P<0.001
Mean
LV
ES
VI
70
50
40
30
20
10
0
60
Repair with
recurrent MR
Repair without
recurrent MR
Replacement
Δ=6.8 ml
Baseline 12 mos
PERCUTANEOUS MV
REPAIR INDICATIONS
WILL CONTINUE TO
EVOLVE AND EXPAND
INTO THE REALM OF
FUNCTIONAL MR
• 1,095 pts* with 3+/4+ MR and HF between 2000 and 2008 (74% FMR, 21% DMR). Rx before 10/2011:
DMR pts (n=226): 84% MV surgery, 16% med RxFMR pts (n=814): 36% MV surgery (77% w/CABG), 64% med Rx
Un-operated pts had lower LVEF (mean 27% vs. 42%, p<0.0001 and higher STS score (median 5.8 vs. 4.0, p<0.001) compared with operated pts.
* Excluded MVA ≤2 cm2, AR ≥2+, aortic peak velocity ≥2.5 m/s, HCM, endocarditis, concomitant AV, Ao or pericardial surgeries, LVAD or OHT.
Prognosis
of un-
operated
pts with 3-
4+ MR and
HF
171 of 474 (36%)
un-operated pts
with FMR and good
echos would have
been eligible for
MitraClip based on
published criteria
Goel SS et al. JACC 2014;63,:185–90
% o
f P
ati
en
ts
100
80
60
40
20
0
Mortality
Surviving pts hospitalized for HF
Years
1
20
2 3 4 5
41
50
29
37
58
68
4650
90
Management of 3-4+ MR with HF
What are the anatomic
criteria for MitraClip?
>2mm
<11mm
<10mm
≤15mm
Non-rheumatic MR originating
from the central 2/3 of the valve
Etiology: degenerative or
functional
Sufficient leaflet tissue for
mechanical coaptation
Protocol anatomic exclusions
Flail gap >10mm
Flail width >15mm
LVIDs >55mm
MVA <4 cm2
Data as of 08/31/2014. Source: Abbott Vascular
Study Population N*
EVEREST I (feasibility) Feasibility 55
EVEREST II (pivotal) Roll-in 60
EVEREST II (pivotal) Randomized 184
EVEREST II (pivotal) Non-randomized high-risk 78
REALISM continued access Non-randomized 899
Compassionate/emergency Non-randomized 66
ACCESS Europe Phase I Non-randomized 567
ACCESS Europe Phase II Non-randomized 286
Commercial Use Commercial 14,232
Total 16,427
Worldwide MitraClip Experience
MitraClip RCTs in Functional MRCOAPT RESHAPE-HF Mitra-Fr
N patients, sites 430 @ 75 US sites 800 @ 50 EU sites 288 @ 18 French sites
Control arm Medical Rx Medical Rx Medical Rx
FMR grade≥3+ (EROA ≥30 mm² and/or Rvol >45
mL by ECL)
≥3+ (EROA ≥30 mm² and/or Rvol >45
mL by ECL)
Sev (EROA >20 mm² + Rvol
>30 mL) by ECL
NYHA class II, III, or ambulatory IV III or ambulatory IV II - IV
Other inclusion criteria
HF hosp within 12 months or BNP
≥300 pg/ml or nT-proBNP ≥1500
pg/ml within 12 months; MV surgery
is not local standard of care
HF hosp within 12 months or BNP ≥350
pg/ml or nT-proBNP ≥1400 pg/ml within
90 days; not eligible for MV surgery
HF hosp within 12 months;
not eligible for MV surgery
LVEF ≥20% - ≤50% ≥15% - ≤40% ≥15% - ≤40%
LV volumes LVESD ≤70 mm LVEDD ≥55 mm -
Primary efficacy
endpoint (superiority)
Recurrent HF hospitalization at 12
months
Death or recurrent HF hospitalization at
12 months
Death or recurrent HF
hospitalization at 12 months
Primary safety
endpoint
(noninferiority)
SLDA, device embolizations,
endocarditis/MS/device-related
complications requiring non-elective
CV surgery, LVAD, OHT
- -
Health economics Assessed Assessed -
Follow-up 5 years 2 years 2 years
• 3 trials randomizing 1,518 patients with
heart failure and secondary (functional) MR
to MitraClip vs. GDMT
• As of September 10th, 2014,
207 patients had been randomized:
- COAPT - 124 pts
- RESHAPE-HF - 37 pts
- Mitra-Fr - 46 pts
A Hot 20 Minutes
Aortic Stenosis
Indications for valve replacement are expanding
Access requirements for TF TAVR are getting smaller
Multiple TAVR devices mean more options and better patient care
Mitral Regurgitation
Degenerative (primary) mitral regurgitation needs early surgical referral
Repair vs replace for medically-optimized symptomatic ischemic mitral regurgitation will be driven by surgeon expertise
Percutaneous mitral valve repair indications will continue to evolve and expand into the realm of functional mitral regurgitation