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Severe Mitral Regurgitation:
Device or Surgery?
Bernard Iung - Hôpital Bichat, Paris
Kardiologie Update – 30th November 2014
Bernard Iung, MD, 2014
Consultancy:
• Abbott
• Boehringer Ingelheim
• Valtech
Speaker’s fee
• Edwards Lifesciences
Disclosures
Prevalence of Mitral Regurgitation
11 911 randomly selected 2881 patients from the
patients with echo Framingham cohort
(Nkomo et al. Lancet 2006;368:1005-11) (Singh et al. Am J Cardiol 1999;83:897-902)
Primary MR
(or Organic MR)
Secondary MR
(or Functional MR)
Valve structure Abnormal Normal
Mechanism Primary valve / subvalvular
lesion
Distortion of the valvular
apparatus due to LV
remodelling
Causes Degenerative / Rheumatic
/ Endocarditis / Other
Ischaemic heart disease
/ Cardiomyopathy
LV dysfunction Consequence Cause
Primary / Secondary MR
Primary MR
3491 patients from the Framingham cohort
• 2.4% had mitral valve prolapse • Mitral regurgitation was severe in 3.5% of them
(Freed et al. N Engl J Med 1999;341:1-7)
• Aetiologies of MR in the Euro Heart Survey (877 patients with MR)
• Prevalence of degenerative mitral regurgitation
7%
9%
4%
5%
14% 61%
Degenerative
Rheumatic
Congenital
Endocarditis
Other
Ischaemic
www.escardio.org/guidelines
Class Level
Mitral valve repair should be the preferred technique when it is expected to be
durable. I C
Surgery is indicated in symptomatic patients with LVEF > 30% and LVESD
< 55 mm. I B
Surgery should be considered in patients with severe LV dysfunction
(LVEF < 30% and/or LVESD > 55 mm) refractory to medical therapy with high
likelihood of durable repair and low comorbidity.
IIa C
Surgery may be considered in patients with severe LV dysfunction (LVEF < 30%
and/or LVESD > 55 mm) refractory to medical therapy with low likelihood of
durable repair and low comorbidity.
IIb C
Indications for surgery in symptomatic severe primary MR
Eur Heart J 2012;33:2451-296
Eur J Cardiothorac Surg 2012;42:S1-S44
www.escardio.org/guidelines
Operative mortality after surgery for MR
Eur Heart J 2012;33:2451-296
Eur J Cardiothorac Surg 2012;42:S1-S44
47 279 patients aged ≥ 75 undergoing isolated mitral valve surgery
between 2000 and 2009 (replacement in 29 919, repair in 17 360)
(Vassileva et al. Circulation 2013;127:1870-6)
Late Survival after Surgery for MR
Flail gap Flail width
(Feldman T et al JACC 2009; 54 :686-94)
MitraClip® for Primary MR
Device (%) n=184
Control (%) n=95
P
Age (mean) 67.3 years 65.7 years 0.32
Male 62.5 66.3 0.60
Congestive heart failure 90.8 77.9 <0.01
Coronary artery disease 47.0 46.3 >0.99
Myocardial infarction 21.9 21.3 >0.99
Angina 31.9 22.2 0.12
Atrial fibrillation 33.7 39.3 0.42
Cerebrovascular disease 7.6 5.3 0.62
Peripheral vascular disease 6.5 11.6 0.17
Cardiomyopathy 17.9 14.7 0.61
Hypercholesterolemia 61.0 62.8 0.80
Hypertension 72.3 78.9 0.25
Moderate to severe renal disease 3.3 2.1 0.72
Diabetes 7.6 10.5 0.50
Previous cardiovascular surgery 22.3 18.9 0.54
MR Severity: 3+ to 4+ 95.7 92.6 0.48
MR Etiology: Degenerative / Functional 73 / 27 73 / 27 0.81
EVEREST II Randomized Clinical Trial Baseline Demographics & Co-morbidities
(Feldman et al. N Engl J Med 2011;364:1395-1406 )
• 117 pts with severe degenerative MR
Mean Euroscore 15±13% (≥ 20% in 33 pts)
• 30-day mortality 6.0%
• 81% NYHA I-II at 1 yr. (26% before the procedure)
(Reichenspurner et al. Eur J Cardiothorac Surg 2013;44:e280-8)
MitraClip® for Primary MR: ACCESS EU
www.escardio.org/guidelines
Percutaneous techniques
● Percutaneous edge-to-edge procedure may be
considered in patients with symptomatic severe primary
MR who fulfill the echo criteria of eligibility, are judged
inoperable or at high surgical risk by a ‘heart team’,
and have a life expectancy greater than 1 year
(Class IIb Level C)
Eur Heart J 2012;33:2451-296
Eur J Cardiothorac Surg 2012;42:S1-S44
European Society of Cardiology – Euro Heart Survey
Severe Symptomatic MR
Isolated MR
(n=877)
No Severe MR
(n=331)
Severe MR
(n=546)
No Symptoms
n=144
Symptoms
n=396
Intervention
n=203 (51%)
No Intervention
n=193 (49%)
Symptoms
missing
n=6
Severe MR : ≥ 3/4 at Doppler-echocardiography
Symptomatic MR : NYHA Class II or greater
(Mirabel et al. Eur Heart J 2007;28:1358-65)
European Society of Cardiology – Euro Heart Survey
Total No Intervention Intervention
All aetiologies 396 193 203
EuroSCORE, m±SD 12.5±14.6 16.7±17.1 8.6±10.3*
EuroSCORE ≥ 20, n(%) 70 (18%) 50 (26%) 20 (10%)*
Degenerative MR 209 117 92
EuroSCORE, m±SD 14.7±15.4 18.7±17.8 9.6±9.7*
EuroSCORE ≥ 20, n(%) 47 (23%) 37 (32%) 10 (11%)†
Decision to Operate and Risk Score
* p<0.0001
† p<0.001
Secondary Mitral Regurgitation
MR
WORSE MR VOLUME OVERLOAD
LV DILATION
(Levine et al. Curr Cardiol Rep 2002;4:125-9)
www.escardio.org/guidelines
Indications for mitral valve surgery in secondary mitral regurgitation
Class Level
Surgery is indicated in patients with severe MR undergoing CABG, and
LVEF > 30%. I C
Surgery should be considered in patients with moderate MR undergoing
CABG*. IIa C
Surgery should be considered in symptomatic patients with severe MR,
LVEF < 30%, option for revascularization, and evidence of viability. IIa C
Surgery may be considered in patients with severe MR, LVEF > 30%,
who remain symptomatic despite optimal medical management
(including CRT if indicated) and have low comorbidity, when
revascularization is not indicated.
IIb C
* Exercise echo is recommended to identify dyspnea, increase in severity of MR and in SPAP
Eur Heart J 2012;33:2451-296
Eur J Cardiothorac Surg 2012;42:S1-S44
www.escardio.org/guidelines
Background in the Management
(Moderate-Severe) Secondary MR
1. Operative mortality is higher than in primary MR
2. Long-term prognosis is worse (comorbidities)
3. No evidence that surgery prolongs life (5-yrs death 50%)
1. CABG alone does not correct MR in most patients
2. Untreated MR is associated with recurrent HF and death
3. Functional improvement uniformly reported after MVS
4. Persistence and high recurrence rate of MR after MV repair
Non randomized observational
trials for most
Retrospective trials
One randomized study not powered to evaluate the outcome has compared
CABG with CABG/MVRepair in moderate ischaemic MR
Improvement in class/LV function (Fattouch et al. JTCS 2009;138:278-85)
• 301 pts with multivessel CAD and ischaemic MR
(ERO 0.2 to 0.4 cm², vena contracta 3 to 7 mm)
• Randomized to CABG + valve repair vs. CABG
• LVESVI at 1 yr: 49.6±31.5 ml (CABG+MVR) vs.46.1±22.4 ml/m² (CABG alone) (p=0.61)
(Smith et al. N Engl J Med 2014;Nov.18)
Surgery for Ischaemic MR
• 251 pts with severe ischaemic MR (ERO >0.4 cm²)
• Randomized to valve repair or replacement ± CABG
• LVESVI at 1 yr: 61.1±26.2 ml/m² (repair) vs. 65.7±27.4 ml/m² (replacement) (p=0.18)
(Acker et al. N Engl J Med 2014;370:23-32)
Repair / Replacement for Ischaemic MR
•
(Feldman T et al JACC 2009; 54 :686-94)
Coaptation length Coaptation depth
MitraClip® for Secondary MR
ACCESS EUROPE Registry
EVEREST II RCT Device Patients
N=178
ACCESS EU MitraClip Patients
N=567
Age (yrs), mean±SD 67 ± 13 74 ± 10
Logistic EuroSCORE, (%)
Mean ± SD NA 23 ± 18
EuroSCORE ≥ 20% (%) NA 45
Coronary Artery Disease (%) 47 63
NYHA Functional Class III or IV (%) 50 85
Mitral Regurgitation Grade ≥3/4 (%) 96 98
Ejection Fraction < 40% (%) 6 53
Secondary MR (%) 27 77
Ischaemic NA 42
Non-ischaemic NA 58
Degenerative MR (%) 73 23
(Maisano et al. J Am Coll Cardiol 2013;62:1052-61)
ACCESS EUROPE Registry
• Mortality
− 3.4% at 30 days
− 17.3% at 1 year
• Mitral regurgitation
• Functional class 71.4% NYHA I-II at 1 year (15.1% before the procedure)
(Maisano et al. J Am Coll Cardiol 2013;62:1052-61)
EVEREST High-Risk + REALISM
N=351
Age (yrs), mean±SD 76 ± 10
STS score (%) 11.3 ± 7.7
STS > 12% (%) 43
Coronary Artery Disease (%) 82
NYHA Functional Class III or IV (%) 85
Mitral Regurgitation Grade ≥3/4 (%) 100
Ejection Fraction < 40% (%) 47 ±1 4
Secondary MR (%) 70
Degenerative MR (%) 30
• MR ≥ 3/4
• and high-risk: STS ≥ 12 % or predefined comorbidity
(Glower et al. J Am Coll Cardiol 2014;64:172–81)
MitraClip® in High-Risk Patients
• Mortality
− 4.8% at 30 days
− 22.8% at 1 year
• Late survival MR grade (223 pts)
(Glower et al. J Am Coll Cardiol 2014;64:172–81)
MitraClip® in High-Risk Patients
www.escardio.org/guidelines
Percutaneous techniques
● The percutaneous mitral clip procedure may be considered
in patients with symptomatic severe secondary MR despite
optimal medical therapy (including CRT if indicated), who
fulfil the echo criteria of eligibility, are judged inoperable or
at high surgical risk by a team of cardiologists and cardiac
surgeons, and who have a life expectancy > 1 year
(Class IIb Level C)
“These findings have to be confirmed in larger series
with longer follow-up and with a randomized design”
Eur Heart J 2012;33:2451-296
Eur J Cardiothorac Surg 2012;42:S1-S44
Optimal Valve morphology
Central pathology in segment 2
No leaflet calcification
Mitral valve opening area >4cm²
Mobile length of the posterior leaflet ≥10mm
Coaption depth <11mm
Normal leaflet strength and mobility
Flail-width <15mm Flail-gap <10mm
(Boekstegers et al. Clin Res Cardiol 2014;103:85–96)
Anatomy and Patient Selection
Ideal morphologies for a MitraClip implantation
(Wunderlich and Siegel. Eur Heart J Cardiovasc Imag 2013;14:935-9)
Conditionally suitable valve morphology
Pathology in segment 1 or 3
Mild calcification outside of the grip-zone of the clip system; ring
calcification, post annuloplasty
Mitral valve opening area >3cm² with good residual mobility
Mobile length of the posterior leaflet 7-<10mm
Coaption depth ≥11mm
Leaflet restriction in systole (Carpentier IIIB)
Flail-width >15mm only with a large ring width and the option for
multiple clips
Only in experienced centres
(Boekstegers et al. Clin Res Cardiol 2014;103:85–96)
Anatomy and Patient Selection
(Boekstegers et al. Clin Res Cardiol 2014;103:85–96)
Unsuitable valve morphology
Perforated mitral valve leaflet or cleft
Severe calcification in the grip-zone
Haemodynamically significant mitral stenosis (valve opening
area <3cm², MPG ≥5mmHg)
Mobile length of the posterior leaflet <7mm
Rheumatic leaflet thickening and restriction in systole and
diastole (Carpentier IIIA)
Barlow’s syndrome with multisegment flail leaflets
Anatomy and Patient Selection
Unsuitable morphologies for a
MitraClip implantation
Large Commissural
prolapse
Severe Bivalvular
prolapse
Bichat
Bichat
• MR is frequent and represents a significant burden in the
elderly.
• Surgery remains the reference treatment of primary MR.
• Approximately half of patients with severe, symptomatic
MR are denied surgery.
• High-risk patients (EuroSCORE ≥ 20) account for 1 out of
4 patients with degenerative severe MR and 1 out 3 of
those denied for surgery.
• Percutaneous techniques can be used in less favourable
anatomical conditions.
Conclusion (I)
• Indications for surgery are more restrictive for secondary
mitral regurgitation.
• The availability of lower-risk procedures is of particular
interest for secondary MR.
• Preliminary results of percutaneous interventions are
promising, but randomized trials are needed (and ongoing).
• Prospective population-based studies are also needed to
assess the number of potential candidates for
percutaneous techniques.
Conclusion (II)
251 high-risk patients
with severe MR
-139 transcatheter
-53 surgical
-59 conservative
(Swaan et al.
J Am Coll Cardiol Intv
2014;7:875–81)
(Swaan et al. J Am Coll Cardiol Intv 2014;7:875–81)
Propensity analysis vs. conservative therapy
-Transcatheter HR 0.41 |0.22-0.78], p=0.006
-Surgery HR 0.52 [0.30-0.88], p=0.014
Temporal Changes in
MitraClip indication
4932
www.escardio.org/guidelines
Echocardiographic criteria for the definition of severe valve regurgitation: an integrative approach
Aortic regurgitation Mitral regurgitation Tricuspid
regurgitation
Qualitative
Valve
morphology
Abnormal/flail/large
coaptation defect
Flail leaflet/ruptured papillary
muscle/large coaptation defect
Abnormal/flail/large
coaptation defect
Colour flow
regurgitant jet
Large in central jets,
variable in eccentric jets
Very large central jet or
eccentric jet adhering, swirling,
and reaching the posterior wall
of the left atrium
Very large central jet or
eccentric wall impinging
jet
CW signal of
regurgitant jet
Dense Dense/triangular Dense/triangular with
early peaking (peak vel
< 2 m/s in massive TR)
Other Holodiastolic flow reversal
in descending aorta
(EDV > 20 cm/s)
Large flow convergence zone –
Adapted from Lancellotti, EAE Recommendations. Eur J Echocardiogr. 2010;11:223-244 and 307-332
Eur Heart J 2012;33:2451-296
Eur J Cardiothorac Surg 2012;42:S1-S44
www.escardio.org/guidelines
Aortic regurgitation
Mitral regurgitation Tricuspid
regurgitation
Semiquantitative
Vena contracta width (mm)
> 6 ≥ 7 (> 8 for biplane) ≥ 7
Upstream vein flow – Systolic pulmonary vein flow reversal
Systolic hepatic vein flow reversal
Inflow – E-wave dominant ≥ 1.5 m/s E-wave dominant ≥ 1 m/s
Other Pressure half-time < 200 ms
TVI mitral/TVI aortic > 1.4 PISA radius > 9 mm
Quantitative Primary Secondary
EROA (mm²) ≥ 30 ≥ 40 ≥ 20 ≥ 40
R Vol (ml/beat) ≥ 60 ≥ 60 ≥ 30 ≥ 45
+ enlargement of cardiac chambers/ vessels
LV LV, LA RV, RA, inferior vena cava
Echocardiographic criteria for the definition of severe valve regurgitation: an integrative approach
Adapted from Lancellotti, EAE recommendations. Eur J Echocardiogr. 2010;11:223-244 and 307-332
Eur Heart J 2012;33:2451-296
Eur J Cardiothorac Surg 2012;42:S1-S44
Ischaemic MR After MI
Community-Based Study
• 773 patients undergoing echocardiography within 30 days
following myocardial infarction (mean 3 days)
− 50% ≥ mild MR
− 12% moderate or severe MR
• Ischaemic MR was a predictor of death in multivariate
analysis: adjusted HR 1.55 [1.08-2.22] p=0.019
(Bursi et al. Circulation 2005;111:295-301)
• But subject to changes with LV remodelling
Prevalence of Secondary MR in Chronic
Heart Failure with Impaired LVEF
n= Age
(yrs)
LVEF
(%)
Ischaemic
Dis. (%)
MR Severity
Varadarajan
(JASE 2006)
370 65 21 94 15% grade 3/4
14% grade 4/4
Rossi
(Heart 2011)
1256 67 32 73 24% ERO ≥0.20 cm²
or Reg.vol >30 ml
Agricola (Int J
Cardiol 2011)
198 66 33 65 50% ERO ≥0.20 cm²
Bursi (Eur J
Heart Fail 2010)
469 60 30 95 30% grade 3/4
14% grade 4/4
Deja
(Circulation 2012)
1212 60 27 64 18% moderate or
severe
Estimated Burden of Secondary MR
• ≥ 20% of severe secondary MR in patients with chronic
heart failure due to ischaemic or non-ischaemic
cardiomyopathy
• Estimation of 6 million adults with heart failure in the US,
with 45% of them due to LV dysfunction (Bursi et al. JAMA 2006;296:2209-16)
(Go et al. Circulation 2013;127:e6-e245)
• Estimation of ≥ 500 000 adults with chronic severe
secondary MR in the US
© 2014 Abbott. All rights reserved. AP2939842-OUS Rev. C (08/2014) - 9-EH-4-3874-01 08-2014 REV H
48 Information contained herein intended for use in EMEA
*Data as of 31/7/2014. Source: Abbott Vascular
Study Population N*
EVEREST I (Feasibility) Feasibility patients 55
EVEREST II (Pivotal) Pre-randomized patients 60
EVEREST II (Pivotal) Non-randomized patients
(High Risk Study)
78
EVEREST II (Pivotal) Randomized patients
(2:1 Clip to Surgery)
279
184 Clip
95 Surgery
REALISM (Continued Access) Non-randomized patients 899
Compassionate/Emergency Use Non-randomized patients 66
ACCESS Europe Phase I Non-randomized patients 567
ACCESS Europe Phase II Non-randomized patients 286
Commercial Use Commercial patients 13,738
Total 15,933
+95 surgery
Worldwide Experience in July 2014
Commercial Investigational Special Access
1. First-time procedures only. Includes commercial patients, ACCESS I and ACCESS II patients.
2. Successful implants only. Includes commercial patients, ACCESS I and ACCESS II patients.
3. Successful implants only.
MitraClip Therapy Current Global Adoption
Treating Centers 219
Patients (clinical and real-
world) 6,839
Patients1 (real-world) 5,644
Implant Rate2 96%
Acute MR reduction2,3 98% of
implants
Functional MR2 67%
Degenerative MR2 24%
Mixed2 9%
Mitraclip therapy
Combination of
Techniques
Transcatheter Mitral Valve Implantation
EndoValve CardiAQ( n=3) Medtronic
Neovasc – Tiara( n=3) Lutter Valve (n=2)
Challenges Positioning Fixation Paravalvular leaks Valve gradient and LV outflow track obstruction Thrombosis Durability Feasibility of reintervention …….
Fortis (n=8)
(Lubos et al. J Am Coll Cardiol Intv 2014;7:394–402)
300 high risk patients unsuccessfully treated (discharge MR grade of >2)
a TMPG ≥4 mm Hg, an EROA >70.8 mm2, and an MVOA < 3.0 cm2 carry an
increased risk of acute procedural failure
European Society of Cardiology – Euro Heart Survey
Factors Associated with a Decision
not to Operate on Symptomatic MR
p OR [95% CI]
LV ejection fraction (per 10% decrease)
0.0002 1.39 [1.17 – 1.66]
Aetiology Ischemic Non-ischemic
0.0006 1
4.44 [1.96 – 10.76]
Age (per 10-year increase)
0.001 1.40 [1.15 – 1.72]
Charlson comorbidity index (per 1 point increase)
0.004 1.38 [1.12 – 1.72]
Degree of MR Grade 4/4 Grade 3/4
0.005 1
2.23 [1.28-3.29]
(Mirabel et al. Eur Heart J 2007;28:1358-65)
ACC/AHA Recommendations for
chronic primary MR
Recommendations COR LOE
Transcatheter mitral valve repair may be considered
for severely symptomatic patients with chronic
severe primary MR who have a reasonable life
expectancy but a prohibitive surgical risk because
of severe comorbidities
IIb
B
Nishimura et al. 2014 AHA/ACC Guideline for the Management of Patients
With Valvular Heart Disease. Circulation 2014;129:e521-643
Unsuitable morphologies for a MitraClip implantation
(Wunderlich and Siegel. Eur Heart J Cardiovasc Imag 2013;14:935-9)
• MR grade (223 pts)
• Functional class
(233 pts)
(Glower et al. J Am Coll Cardiol 2014;64:172–81)
MitraClip® in High-Risk Patients