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Mitral Valve Disease
August 29, 2019
Summa internal medicine residents
Justin M. Dunn, MD, MPH
1. Mitral Stenosis
2. Mitral Regurgitation
Outline
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48yo F, presents with 3 weeks progressive dyspnea with associated orthopnea and mild LE edema.
Denies chest pressure, palpitations.
Complains of decreased urine output for 1 week.
Has not seen a physician for many years.
Case
3
On exam, in mild distress with dyspnea and tachypnea.
Heart rate 120, irregular; BP 100/65.
Opening snap heard at left lower sternal border just after S2, with short interval between S2 and snap, followed by mid diastolic murmur at apex (heard best in L lateral position).
Positive JVD to jaw at 90 degrees.
2+ edema bilaterally, cool extremities.
Case
Summa Health Sample Preso 06.06.20165
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ECG revealed afib with HR of 125, no ischemic changes.
Echo revealed doming appearance of the anterior leaflet of the mitral valve, restricted motion of the posterior leaflet, and fusion of the leaflets at both commissures. Peak/mean gradient 34/20.
Case
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Mitral Stenosis
1. Rheumatic disease is the leading cause of MS worldwide.
2. Other etiologies: severe MAC, ESRD, endocarditis, inflammatory disorders, radiation therapy, LA myxoma.
3. Slowly progressive, eventually leads to left atrial enlargement, afib, pulmonary hypertension, decreased cardiac output.
4. 10 year mortality of 70% (untreated) after symptom onset.
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Case
87yo M with DM, HTN, HLD, CKD stage IV, CAD s/p CABG presents with worsening exertional dyspnea for 12 months associated with orthopnea and LE edema.
Physical exam revealed afib with HR 80, BP 110/75.
3/6 holosystolic murmur best heard at apex radiating to axilla and spine, augmented by handgrip and diminished by Valsalva, diminished S1, widely split S2
JVD at 90 degrees
Summa Health Sample Preso 06.06.201625
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Summa Health Sample Preso 06.06.201626
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Classification of MR – 2 Types
Incompetent mitral
valve closure
Systolic retrograde blood flow
from the LV into the LA
Mayo Clinic (www.mayoclinic.com)
Primary:Anatomic abnormality
the mitral valve
• Leaflets
• Subvalvular
apparatus
• Chordae and
papillary muscles
Secondary :LV dilation; often
secondary to ischemic
heart disease
• Leads to mitral
annular dilation
• Incomplete coaptation
of the mitral valve
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Mitral Regurgitation
1. Primary MR
• Most commonly due to myxomatous (degenerative) disease or mitral valve prolapse (e.g. Barlow’s Disease), rheumatic disease in developing countries.
2. Secondary MR
• Referred to as “functional” or “ischemic” MR
• Result of disordered LV geometry
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Structural Heart Disease
Increases with Age
Nkomo et al. Burden of Valvular Heart Diseases: A Population-based Study, Lancet, 2006; 368: 1005-11.
> 9.3% for ≥75 year olds (p<.0001)
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12
10
8
6
4
2
0Pre
vale
nce
(%
) o
f m
od
erat
e to
se
vere
val
ve d
ise
ase
Aortic valve disease
Age (years)
<45 45-54 55-64 65-74 >75
Mitral valve disease
All valve disease
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Stages of Primary MR
Stages of Secondary MR
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Asymptomatic DMR
Natural History
Avierinos JF, et al. Circulation 2002;106:1355
100
90
80
70
60
50
Surv
ival
%
0 2 4 6 8 10
2 RF
1 RF
95 ±2
70 ±5
55 ±9
Risk Factors
Age 50 yrs
Atrial fibrillation
LA enlargement
Flail
MR 3
or
EF <50%
Years after diagnosis
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Asymptomatic Primary MR
Severity and Survival
Enriquez-Sarano M et al. NEJM 2005;352:875-83
Worse Survival
100
90
80
70
60
50
0
Surv
ival
(%
)
Years
0 1 2 3 4 5
P<0.01
ERO <20mm2 (91 ±3%)
ERO 40mm2 (58 ±9%)
ERO 20-39mm2 (66 ±6%)
More CV Events
70
60
50
40
30
20
10
0
Rat
e o
f C
ard
iac
Even
ts %
Years
0 1 2 3 4 5
P<0.01
ERO <20mm2 (15 ±4%)
ERO 20-39mm2
(40 ±7%)
ERO 40mm2 (62 ±8%)
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EF and Surgical Outcome
100
80
60
40
20
0
Surv
ival
%
Years
0 1 2 3 4 5 6 7 8 9 10
EF 60%
EF 50-60%
EF <50%
P=0.0001
72 ±4%
53 ±9%
EF <60% is Abnormal in MR
32 ±12%
Enriquez-Sarano M, et al., Circulation 1994;90:830-837
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Symptoms and Surgery
Outcome with Primary MR
100
80
60
40
20
0
Surv
ival
%
Years
0 1 2 3 4 5 6 7 8 9 10
NYHA I-II
NYHA III-IV
P<0.0001
90 ±276 ±5
73 ±3
48 ±4
Tribouilly CM et al., Circulation 1999;99:400-5
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Flail Mitral Leaflet
Natural History
Ling L, et al. N Engl J Med 1996; 335:1417-1423
100
80
60
40
20
0
Surv
ival
%
Years After Diagnosis
0 1 2 3 4 5 6 7 8 9 10
P<0.001
Class I or II
Class III or IV
Mortality4% per year
34% per year
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• Papillary muscle
displacement
Trichon BH, et al. Am J Cardiol 2003;91:538-43
Secondary Mitral Regurgitation
A Ventricular Problem
Regional or
Global Dysfunction
• Annular flattening
• Leaflet tethering
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Secondary Mitral Regurgitation
A Harbinger of Poor Outcome
Two-fold Increase Risk of DeathGrigioni F, et al. Circulation 2001;103:1759-64; Basket JF, et al. Can J Cardiol 2007;23:797-800
1.0
0.8
0.6
0.4
0.2
0.0
Surv
ival
(%
)
Years
0 1 2 3 4 5
P<0.001
50
40
30
20
10
0D
eath
or
hea
rt f
ailu
re
ho
spit
aliz
atio
n %
Follow-up time (days)
0 365 730 1095
P=0.0006
MI w/o MR
MI with MR
61 ±6
38 ±5
MitralRegurgitation
No Mitral Regurgitation
Post-MI SOLVD (EF >35%)
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Hospitalization-free survival decreased
with increased MR severity1
100
80
60
40
20
0
Ho
spit
aliz
atio
n-f
ree
Surv
ival
(%
)
Years
0 1 2 3 4 5 6 7
P<0.01
No MR(40%)
Severe MR 7%)
Mild/mod MR(25%)
Transplant-free survival decreased
with increased MR severity2
100
90
80
70
60
50
40
Tran
spla
nt-
free
Su
rviv
al (
%)
Days
0 500 1000 1500 2000
Grade IV(46.5 ±6.7%)
Grade III(68.5 ±4.6%)
Secondary Mitral Regurgitation
Increased Severity = Increased Morbidity
1. Rossi A, Dini FL, Faggiano P, et al. Independent prognostic value of functional mitral regurgitation in patients with heart failure: a quantitative analysis of 1256 patients with ischemic and non-ischaemicdilated cardiomyopathy. Heart. 2011;97(20):1675-1680.
2. Bursi F, Barbieri A, Grigioni F, et al. Prognostic implications of functional mitral regurgitation according to the severity of the underlying chronic heart failure: a long-term outcome study. Eur J Heart Fail. 2010;12(4):382-388.
Grade II(64.4 ±4.9%)
No MR & Grade I(82.7 ±3.1%)
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Pathophysiology of MR
Increasing Mitral Regurgitation
Increase Load/Stress
Muscle Damage/Loss
Dysfunctionof Left Ventricle
Dilation ofLeft Ventricle
1 year
mortality
up to
57%1
1 Cioffi G, et al. Functional mitral regurgitation predicts 1-year mortality in elderly patients with systolic chronic heart failure. European Journal of Heart Failure 2005 Dec;7(7):1112-7
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General Principles of Therapy
Primary
Surgery for symptoms or LV dysfunction
Secondary
Asymptomatic if repairable and low risk
Medical therapy first
No medical option for valve
Consider CRT
Surgery only in highly selected patients with HF
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Current Therapy Considerations
Medical Therapy
Less Invasive
Increased MR Reduction
MV SurgeryMitraClip®
*Reference Source: Instructions For Use
See important safety information referenced within
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Timing of Surgical Intervention
ACC/AHA Guidelines – Primary MR
Consider surgery when
Symptoms
or
LV dysfunction (EF<60%, ESD≥40 mm)Try to repair
Nishimura R, et al., J Am Coll Cardiol 2014;63:2438-88
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Timing of Surgical Intervention
ACC/AHA Guidelines – Primary MR
Prophylactic Repair
likelihood of success >95%
and
mortality rate <1%
Can be done if
Nishimura R, et al., J Am Coll Cardiol 2014;63:2438-88
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Early Surgery Is Better
Patients without Class I Indications
100
80
60
40
20
0
Surv
ival
%
Follow-up, y
0 5 10 15 20
Suri R et al., JAMA 2013;310:609-16
Early surgery
Medical management
Log-rank P<.001
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Surgical Intervention
ACC/AHA Guidelines – Secondary MR
Surgery may be considered for severe symptoms despite optimal GDMT for HF (IIb)
Also for other CV surgery if severe (IIa) or moderate (IIb)
Nishimura R, et al., J Am Coll Cardiol 2014;63:2438-88
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Surgery for Secondary MR
Wu AH, et al. J Am Coll Cardiol 2005;45:381-87
No Mortality Benefit
1.0
0.8
0.6
0.4
0.2
0.0
Even
t-fr
ee S
urv
ival
Time (Days)
0 500 1000 1500 2000
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MitraClip® System
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Randomize 1:1
Clinical and TTE follow-up:
Baseline, Treatment, 1-week (phone)1, 6, 12, 18, 24, 36, 48, 60 months
Control groupStandard of care
N=215
Symptomatic heart failure subjects who are treated per standard of care Determined by the site’s local heart team as not appropriate for mitral valve surgery
Specific valve anatomic criteria
MitraClip
N=215
Significant FMR (≥3+ by core lab)
COAPT Trial Design
Goals: 430 patients at up to 75 US sites
Clinical Investigational Plan 11-512: Version 5.1, November 11, 2013. COAPT protocol approved by FDA July 27, 2012
Thank you
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