Successfully reported this slideshow.
We use your LinkedIn profile and activity data to personalize ads and to show you more relevant ads. You can change your ad preferences anytime.
Functional Mitral Regurgitation:
Definitions, Causes, Natural History, and
Interventions
Heart Failure Management 2015
Ame...
All Rights Reserved, Duke Medicine 2007
Presenter Disclosure Information
“Functional Mitral Regurgitation:
Definitions, Ca...
All Rights Reserved, Duke Medicine 2007
Moderate or Severe MR Is Common; Increases With Age
Mitral regurgitation is the mo...
All Rights Reserved, Duke Medicine 2007
Mitral Valve Anatomy: Surgical View from Above
4
All Rights Reserved, Duke Medicine 2007
Carpentier Classification of MR: Leaflet Motion
Normal leaflet
motion
Prolapse or
...
All Rights Reserved, Duke Medicine 2007
Degenerative vs Functional MR
MR
Primary MR
(DMR)
Myxomatous
Degeneration
(DMR) (9...
All Rights Reserved, Duke Medicine 2007
Secondary MR: a rose by any other name….
• Functional MR (vs. Degenerative)
• Seco...
All Rights Reserved, Duke Medicine 2007
Secondary
MR
(FMR)
Dilated
Annulus
Normal LVEF
Inferobasal
MI
Normal LVEF
Dilated ...
All Rights Reserved, Duke Medicine 2007
Proposed Mechanism of Functional MR
From Otsuji et al, Circulation 1997
9
All Rights Reserved, Duke Medicine 2007
Pathology of FMR is Complex and Heterogeneous
• Coronary Artery Disease
– Ischemic...
All Rights Reserved, Duke Medicine 2007
Severe MR Criteria Different for Primary vs Secondary MR
11
All Rights Reserved, Duke Medicine 2007
Relationship between EROA, RVol, & LVEDV
12Grayburn P et al, J Am Coll Cardiol 2015
All Rights Reserved, Duke Medicine 2007
Secondary MR: ACC/AHA Guideline Classification
Nishimura R et al. ACC/AHA Guidelin...
All Rights Reserved, Duke Medicine 2007
Prognosis of MR in Post MI LVSD – SAVE Trial
Lamas, et al, Circulation 1997; 96:82...
All Rights Reserved, Duke Medicine 2007
FMR at Duke: Survival by Severity at 1, 3, 5 and 10 years
0
10
20
30
40
50
60
70
8...
All Rights Reserved, Duke Medicine 2007
FMR Severity and Mortality in CABG Eligible Patients
Deja M. et al. Circulation 20...
All Rights Reserved, Duke Medicine 2008
Severe MR in symptomatic patients
5737 pts with ≥3+ MR
• ~20% HF symptoms
• Primar...
All Rights Reserved, Duke Medicine 2007
Therapeutic Approaches – Lots of
Questions, Limited Answers
• What should we do ab...
All Rights Reserved, Duke Medicine 2008
CRT Can Reduce FMR
Circ 2011;124:912-919.
AND REDUCED MR IS
ASSOCIATED WITH
LOWER ...
All Rights Reserved, Duke Medicine 2007
Low EF and Moderate to Severe FMR with CAD
Effect of treatment vs. medical therapy...
All Rights Reserved, Duke Medicine 2007
STICH Trial Moderate- Severe MR- Effect of MVR
Deja, et al, Circulation 2012 21
CTSN Severe MR Trial Design
Acker M, et al, N Engl J Med 2013
Median change in LVESVI
ChangeinLVESVI(mm/m2)
Repair Replacement Repair Replacement
(All pts) (All pts) (Survivors) (Survi...
Recurrent MR at 1 year
32.6
2.3
0
5
10
15
20
25
30
35
Repair Replacement
Percentwithmoderateorsevere
recurrentMR
Moderate ...
Patients Screened for Moderate Ischemic MR
(n=6,676)
Randomized Patients
(n=301)
Primary Endpoint Analysis
(n=301)
CABG + ...
CABG Alone
CABG + MV
Repair
P-value
No. of Grafts 3.3±0.9 3.2±0.9 NS
Aortic XClamp (min) 74.7±36.7 117.2±35.4 <0.001
CPB t...
Z=0.50, p=0.61
(All patients)
Change in LVESVI at 1 Year
CABG
Alone
CABG +
MV Repair
CABG
Alone
CABG +
MV Repair
(All Pati...
MACCE at 12 Months
CTSN II - Mitral Regurgitation
0
5
10
15
20
25
30
35
40
45
50
SF-12 (Physical Function) MLHF
MeanScore
CABG Alone
CABG + MV Repair
Δ = 14%
Δ = 45% Δ = 48...
All Rights Reserved, Duke Medicine 2007
Mitra-Clip Edge-to-Edge Repair
All Rights Reserved, Duke Medicine 2007
Percutaneous Approaches to MR
MitraClip Aligned MitraClip Deployed
32
All Rights Reserved, Duke Medicine 2007
Grasp
All Rights Reserved, Duke Medicine 2007
MitraClip Reduces MR
Before MitraClip After MitraClip
34
All Rights Reserved, Duke Medicine 2008
EVEREST II Randomized Control
Trial of MitraClip® vs. Surgical Repair
• 279 pts at...
All Rights Reserved, Duke Medicine 2008
EVEREST II
MR Severity at One Year
0
10
20
30
40
50
60
0 1+ 2+ 3+ 4+
MR Grade
Mitr...
All Rights Reserved, Duke Medicine 2007
EVEREST II RCT – Changes in NYHA FC
37
Mauri L et al, J Am Coll Cardiol 2013
All Rights Reserved, Duke Medicine 2007
EVEREST II RCT – Freedom from Death & MV Surgery
38Mauri L et al, J Am Coll Cardio...
All Rights Reserved, Duke Medicine 2007
EVEREST II High Risk Registry:
12 month Survival
39
Glower D, et al, J Am Coll Car...
All Rights Reserved, Duke Medicine 2007
EVEREST II High Risk Registry:
MR Grade & NYHA Functional Class
40
Glower D, et al...
All Rights Reserved, Duke Medicine 2007
MitraClip vs. Natural History Among High Risk
- propensity matched comparison
41
V...
All Rights Reserved, Duke Medicine 2007
Length = 7.0
cm
LV
LA
LV
LA
RV
RA
LV
RV
LA
All Rights Reserved, Duke Medicine 2007
Mean PG = 1.7
mmHg
LVEDD = 5.6
cm
All Rights Reserved, Duke Medicine 2008
MitraClip in CRT Non-Responders
N=51, age 70, LVEF 27%, NT-BNP 3702
NYHA MR
Auricc...
All Rights Reserved, Duke Medicine 2007
Ongoing RCTs of MitraClip in HF patients with FMR
45Asgar AW et al, J Am Coll Card...
All Rights Reserved, Duke Medicine 2007
ACC/AHA Recommendations for Secondary MR
46
Recommendations COE LOE
MV surgery is ...
All Rights Reserved, Duke Medicine 2008
Transcatheter MV Replacement?
Circ 2014;130;1712-22.
ACC/AHA Clinical Practice Guidelines
Proportion of Recommendations with Level of Evidence A
11.7%
26.4%
15.3%
13.5%
12.0%
...
All Rights Reserved, Duke Medicine 2007
Conclusions: Functional Mitral Regurgitation
• FMR is a disease of the left ventri...
Upcoming SlideShare
Loading in …5
×

Functional Mitral Regurgitation: Definitions, Causes, Natural History, and Interventions

3,606 views

Published on

Eric J. Velazquez, MD
Duke University Medical Center

Published in: Health & Medicine

Functional Mitral Regurgitation: Definitions, Causes, Natural History, and Interventions

  1. 1. Functional Mitral Regurgitation: Definitions, Causes, Natural History, and Interventions Heart Failure Management 2015 Amelia Island – July 15 2016 Eric J. Velazquez, MD, FACP, FACC, FASE, FAHA Professor of Medicine Chief, Cardiovascular Imaging Section Director, Cardiac Diagnostic Unit & Echocardiography Laboratories Director, DCRI Late Phase Cardiovascular Trials Duke University Health System & Duke Clinical Research Institute
  2. 2. All Rights Reserved, Duke Medicine 2007 Presenter Disclosure Information “Functional Mitral Regurgitation: Definitions, Causes and Natural History” • I will not discuss off label use or investigational use in my presentation. • I have financial relationships to disclose: • Employee of: Duke University • Consultant for: Novartis, Merck, Amgen • Research support from: National Institutes of Health, Novartis, Pfizer, Alnylam, Amgen, Bay Labs 2
  3. 3. All Rights Reserved, Duke Medicine 2007 Moderate or Severe MR Is Common; Increases With Age Mitral regurgitation is the most common type of heart valve insufficiency in the US1,2 – Prevalence increases with increasing age, from 0.5% for 18-44 yr olds rising to 9.3% for ≥75 year olds (p<.0001) 1. Heart Disease and Stroke Statistics 2010 Update: A Report From the American Heart Association. Circulation 2010;121:e46-215. 2. Nkomo VT et al. Lancet 2006; 368:1005-1011. Prevalence of Valvular Heart Disease by Age 3
  4. 4. All Rights Reserved, Duke Medicine 2007 Mitral Valve Anatomy: Surgical View from Above 4
  5. 5. All Rights Reserved, Duke Medicine 2007 Carpentier Classification of MR: Leaflet Motion Normal leaflet motion Prolapse or flail leaflet Leaflet restriction systole & diastole Leaflet restriction systole only Endocarditis Dilated annulus -Atrial fibrillation -Restrictive CM MVP Papillary rupture Trauma Rheumatic SLE Radiation Drugs Ischemic Heart Disease Dilated CM 5
  6. 6. All Rights Reserved, Duke Medicine 2007 Degenerative vs Functional MR MR Primary MR (DMR) Myxomatous Degeneration (DMR) (90%) Other (10%) Rheumatic, post- inflammatory, radiation, drugs, etc Secondary MR (FMR) Mitral valve is structurally normal for age Type II Type IIIa Type I or Type IIIb 6 ~ 90%~ 10%
  7. 7. All Rights Reserved, Duke Medicine 2007 Secondary MR: a rose by any other name…. • Functional MR (vs. Degenerative) • Secondary MR (vs. Primary) • Ischemic MR (vs. Non-Ischemic) • Mitral regurgitation that occurs in the setting of left ventricular dysfunction with normal (or nearly normal) mitral leaflet and chordal structure 7
  8. 8. All Rights Reserved, Duke Medicine 2007 Secondary MR (FMR) Dilated Annulus Normal LVEF Inferobasal MI Normal LVEF Dilated LV Low LVEF Nonischemic DCM Ischemic DCM HF and Secondary MR 8
  9. 9. All Rights Reserved, Duke Medicine 2007 Proposed Mechanism of Functional MR From Otsuji et al, Circulation 1997 9
  10. 10. All Rights Reserved, Duke Medicine 2007 Pathology of FMR is Complex and Heterogeneous • Coronary Artery Disease – Ischemic vs Nonischemic etiology • Left Ventricle – Global vs regional wall motion abnormalities – Dilated or non-dilated • Mitral Annulus – Normal, dilated, calcified – Symmetric or asymmetric dilation • Electrical Activation – MR reduction occurs with CRT in some patients • Dynamic – Preload and afterload sensitive 10
  11. 11. All Rights Reserved, Duke Medicine 2007 Severe MR Criteria Different for Primary vs Secondary MR 11
  12. 12. All Rights Reserved, Duke Medicine 2007 Relationship between EROA, RVol, & LVEDV 12Grayburn P et al, J Am Coll Cardiol 2015
  13. 13. All Rights Reserved, Duke Medicine 2007 Secondary MR: ACC/AHA Guideline Classification Nishimura R et al. ACC/AHA Guidelines 2014 13
  14. 14. All Rights Reserved, Duke Medicine 2007 Prognosis of MR in Post MI LVSD – SAVE Trial Lamas, et al, Circulation 1997; 96:827-33 No MR MR 14
  15. 15. All Rights Reserved, Duke Medicine 2007 FMR at Duke: Survival by Severity at 1, 3, 5 and 10 years 0 10 20 30 40 50 60 70 80 90 100 1 yr 3 yr 5 yr 10 yr Survival Years None/Trivial Mild Moderate Severe Samad, Z … Velazquez EJ., manuscript under review 15
  16. 16. All Rights Reserved, Duke Medicine 2007 FMR Severity and Mortality in CABG Eligible Patients Deja M. et al. Circulation 2012 16
  17. 17. All Rights Reserved, Duke Medicine 2008 Severe MR in symptomatic patients 5737 pts with ≥3+ MR • ~20% HF symptoms • Primary (degenerative) 26% – Most undergo surgery • Secondary (functional) 74% – Most receive medical therapy J Am Coll Cardiol. 2014;63(2):185-186. doi:10.1016/j.jacc.2013.08.723
  18. 18. All Rights Reserved, Duke Medicine 2007 Therapeutic Approaches – Lots of Questions, Limited Answers • What should we do about patients with moderate or severe FMR and LVSD going to CABG? ─ MV repair or MV replacement? Neither? • What should we do about patients with severe FMR and LVSD but no CAD surgical indication? – MV repair/replacement? Continue medical therapy? MCSD? • What should we do with patients with severe FMR and LVSD who are not otherwise CT surgical candidates? – MitraClip? – Medical therapy only? 18
  19. 19. All Rights Reserved, Duke Medicine 2008 CRT Can Reduce FMR Circ 2011;124:912-919. AND REDUCED MR IS ASSOCIATED WITH LOWER MORTALITY
  20. 20. All Rights Reserved, Duke Medicine 2007 Low EF and Moderate to Severe FMR with CAD Effect of treatment vs. medical therapy - Adjusted Treatment HR 95% CI Chi-Square P Value PCI 0.78 0.61, 1.00 3.83 0.50 CABG surgery 0.56 0.42, 0.76 14.01 <0.001 MV surgery 0.64 0.33, 1.27 1.63 0.202 CABG + MV surgery 0.58 0.44, 0.78 13.26 <0.001 Samad, Z … Velazquez EJ. European Heart J 2016. 20
  21. 21. All Rights Reserved, Duke Medicine 2007 STICH Trial Moderate- Severe MR- Effect of MVR Deja, et al, Circulation 2012 21
  22. 22. CTSN Severe MR Trial Design Acker M, et al, N Engl J Med 2013
  23. 23. Median change in LVESVI ChangeinLVESVI(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) Acker M, et al, N Engl J Med 2013
  24. 24. Recurrent MR at 1 year 32.6 2.3 0 5 10 15 20 25 30 35 Repair Replacement Percentwithmoderateorsevere recurrentMR Moderate or Severe Recurrent MR p < 0.001 Acker M, et al, N Engl J Med 2013
  25. 25. Patients Screened for Moderate Ischemic MR (n=6,676) Randomized Patients (n=301) Primary Endpoint Analysis (n=301) CABG + Valve Repair Undersized Ring (n=150) CABG Alone (n=151) Outcomes Measured at 6, 12 and 24 months CTSN Moderate MR Trial Design Smith P, et al, N Engl J Med 2014
  26. 26. CABG Alone CABG + MV Repair P-value No. of Grafts 3.3±0.9 3.2±0.9 NS Aortic XClamp (min) 74.7±36.7 117.2±35.4 <0.001 CPB time (min) 106.8±49.7 163.1±54.9 <0.001 ICU stay 4.0±5.7 4.8±6.1 0.006 Postoperative LOS 9.4±5.9 11.3±8.2 0.002 Data presented as mean±std Operative Conduct and Length of Stay
  27. 27. Z=0.50, p=0.61 (All patients) Change in LVESVI at 1 Year CABG Alone CABG + MV Repair CABG Alone CABG + MV Repair (All Patients) (Survivors) ChangeinLVESVI(mL/m2) Median with 95% CI for change in LVESVI (1 Year – baseline) Smith P, et al, N Engl J Med 2014
  28. 28. MACCE at 12 Months
  29. 29. CTSN II - Mitral Regurgitation
  30. 30. 0 5 10 15 20 25 30 35 40 45 50 SF-12 (Physical Function) MLHF MeanScore CABG Alone CABG + MV Repair Δ = 14% Δ = 45% Δ = 48% Δ = 12% Δ = Median improvement from baseline to 12 months CTSN – II Quality of Life at 1 year
  31. 31. All Rights Reserved, Duke Medicine 2007 Mitra-Clip Edge-to-Edge Repair
  32. 32. All Rights Reserved, Duke Medicine 2007 Percutaneous Approaches to MR MitraClip Aligned MitraClip Deployed 32
  33. 33. All Rights Reserved, Duke Medicine 2007 Grasp
  34. 34. All Rights Reserved, Duke Medicine 2007 MitraClip Reduces MR Before MitraClip After MitraClip 34
  35. 35. All Rights Reserved, Duke Medicine 2008 EVEREST II Randomized Control Trial of MitraClip® vs. Surgical Repair • 279 pts at 37 sites • ACC/AHA indications for MV repair • >Moderate MR by quantitative, core lab assessment MitraClip Repair (n=184) Surgery Repair or Replacement (n=95) One year outcome Freedom from death, surgery for mitral valve dysfunction, or >moderate mitral regurgitation
  36. 36. All Rights Reserved, Duke Medicine 2008 EVEREST II MR Severity at One Year 0 10 20 30 40 50 60 0 1+ 2+ 3+ 4+ MR Grade MitraClip Surgery N Engl J Med 2011;364:1395-1406
  37. 37. All Rights Reserved, Duke Medicine 2007 EVEREST II RCT – Changes in NYHA FC 37 Mauri L et al, J Am Coll Cardiol 2013
  38. 38. All Rights Reserved, Duke Medicine 2007 EVEREST II RCT – Freedom from Death & MV Surgery 38Mauri L et al, J Am Coll Cardiol 2013 279 randomized – 194 MitraClip (FMR 27%) Age 67/ Women 37.5% HF Hx 91%/ CAD 47% NYHA III/IV 51.1% LVEF 60% 30d – 1.1% 12m – 6.3% 2y – 12.5% 4y – 15.9%
  39. 39. All Rights Reserved, Duke Medicine 2007 EVEREST II High Risk Registry: 12 month Survival 39 Glower D, et al, J Am Coll Cardiol 2014 351 enrolled – FMR 70% Age 75.7/ Women 39.6% HF Hx 98%/ CAD 82.2% NYHA III/IV 84.9% (IV 23.4%) LVEF 47.5% Procedural – 0 (15); 1 (201); 2 (135) 30d – 4.8% 12m – 22.8%
  40. 40. All Rights Reserved, Duke Medicine 2007 EVEREST II High Risk Registry: MR Grade & NYHA Functional Class 40 Glower D, et al, J Am Coll Cardiol 2014
  41. 41. All Rights Reserved, Duke Medicine 2007 MitraClip vs. Natural History Among High Risk - propensity matched comparison 41 Velazquez EJ et al, Am Heart J 2015
  42. 42. All Rights Reserved, Duke Medicine 2007 Length = 7.0 cm LV LA LV LA RV RA LV RV LA
  43. 43. All Rights Reserved, Duke Medicine 2007 Mean PG = 1.7 mmHg LVEDD = 5.6 cm
  44. 44. All Rights Reserved, Duke Medicine 2008 MitraClip in CRT Non-Responders N=51, age 70, LVEF 27%, NT-BNP 3702 NYHA MR Auricchio, JACC, 2011.
  45. 45. All Rights Reserved, Duke Medicine 2007 Ongoing RCTs of MitraClip in HF patients with FMR 45Asgar AW et al, J Am Coll Cardiol 2015
  46. 46. All Rights Reserved, Duke Medicine 2007 ACC/AHA Recommendations for Secondary MR 46 Recommendations COE LOE MV surgery is reasonable for patients with chronic severe MR (stage C/D) who are undergoing CABG or AVR IIa C MV surgery may be considered for severely symptomatic patients (NYHA III/IV) with chronic severe secondary MR (stage D) IIb B MV repair may be considered for patients with chronic moderate secondary MR (stage B) who are undergoing other cardiac surgery IIb C MitraClip may be considered in symptomatic patients with severe secondary MR despite GDMT after careful candidate selection IIb B
  47. 47. All Rights Reserved, Duke Medicine 2008 Transcatheter MV Replacement? Circ 2014;130;1712-22.
  48. 48. ACC/AHA Clinical Practice Guidelines Proportion of Recommendations with Level of Evidence A 11.7% 26.4% 15.3% 13.5% 12.0% 22.9% 6.4% 6.1% 23.6% 0.3% 9.7% 11.0% 19.0% 4.9% 4.8% 0% 10% 20% 30% AF Heart failure PAD STEMI Perioperative Secondary prevention Stable angina SV arrhythmias UA/NSTEMI Valvular disease VA/SCD PCI CABG Pacemaker Radionuclide imaging Tricoci JAMA. 2009;301:831-41.
  49. 49. All Rights Reserved, Duke Medicine 2007 Conclusions: Functional Mitral Regurgitation • FMR is a disease of the left ventricle • FMR and HF occur commonly together • FMR causes LV remodeling, heart failure, death • Vast majority of FMR is treated medically • Therapy that improves LV function likely improves FMR – medical therapy, CRT, CABG; no specific medical therapy approved for MR reduction • Optimal approach to FMR beyond GD therapy for HF/LVSD and CAD remains controversial • Further RCTs needed 49

×