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

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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

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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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