management of valvular heart disease 2016 - ilacc.org heart disease 2016 . evidence-based...

Robert O. Bonow, MD, MS

No Relationships to Disclose

Northwestern University Feinberg School of Medicine

Bluhm Cardiovascular Institute

Northwestern Memorial Hospital

Management of

Valvular Heart Disease

2016

www.acc.org

www.americanheart.org

Evidence-based guidelines?

The majority of recommendations

are Level of Evidence C

Stages of Valvular Heart Disease

Stage

A

B

C

D

Definition

Risk of valve disease

Mild - moderate asymptomatic disease

Severe valve disease but asymptomatic

C1: Normal LV function

C2: Depressed LV function

Severe, symptomatic valve disease

Mitral regurgitation

Degenerative MR: primary valve disease

Functional MR: primary myocardial disease


Primary mitral regurgitation

Secondary mitral regurgitation

Chronic Mitral Regurgitation

Echo findings:

• Dilated left ventricle

• Normal LV systolic function

• Myxomatous leaflets with MVP

• Dilated left atrium

• Normal pulmonary artery pressure

• Severe mitral regurgitation

56 year old healthy man

Chronic Mitral Regurgitation

56 year old healthy man

Issues:

• Surgery?

• Medical therapy?

• Transcatheter repair?


• Symptomatic patients

• Asymptomatic patients

• LV systolic dysfunction

• Pulmonary hypertension

• Atrial fibrillation

• Normal LV function, repair feasible?

?

class I

class I

class IIa

class IIa

Indications for mitral valve surgery

for severe primary MR?








class I

class I

class IIa

class IIa



MV repair to improve survival?

What is the natural history?

?








class I

class I

class IIa

class IIa



66% come to surgery in 5 years because of symptoms,

LV dysfunction, pulmonary hypertension or AF

Asymptomatic severe primary MR:








class I

class I

class IIa

class IIa



Severe primary MR:

Long-term postoperative survival is worse if surgery

is performed after patients become symptomatic

J Thorac Cardiovasc Surg 2003;125:1143-1152

0

20

40

60

80

100

0 1 2 3 4 5 6 7 8 9 10 11

Mitral Regurgitation Survival After Mitral Valve Surgery

40

20

0

Surv

ival (p

erc

ent)

0 2 4 6 8 10 12

Time (years)

Expected

64%

n=488

p<0.001

Surgery for

Acquired

Cardiovascular

Disease

14

100

80

60

David et al, J Thorac Cardiovasc Surg 2003;126:1143-1152


0

20

40

60

80

100

0 1 2 3 4 5 6 7 8 9 10 11


40

20

0

Surv

ival (p

erc

ent)

0 2 4 6 8 10 14 12

Time (years)

David et al, J Thorac Cardiovasc Surg 2003;126:1143-1152

FC I-II

58%

FC III-IV

81%

n=488

p<0.001

Surgery for

Acquired

Cardiovascular

Disease

100

80

60


0

20

40

60

80

100

0 1 2 3 4 5 6 7 8 9 10 11


40

20

0

Surv

ival (p

erc

ent)

2 4 6 8 10 20 12

Time (years)

David et al, Circulation 2013;127:1485-1492

FC I

32%

75%

n=840

p<0.001

0 14 16 18

52%

66% 60

80

100

FC IV

FC III

FC II


class IIa

class I !

Indications for MV repair for

asymptomatic primary MR:

• Repair better than mitral valve replacement

• Patients should be referred to centers experienced in repair

• Chronic severe MR

• Preserved LV function

• Experienced surgical center

• Likelihood of durable repair without residual MR > 95%.


Primary mitral regurgitation


• Diagnostic dilemmas

• Therapeutic dilemmas

Imprecision in grading severity of secondary MR

What is “severe”

secondary MR?

0

20

40

60

80

100

1 2 3 4 5 6 7 8

Surv

ival (p

erc

ent)

40

20

0

Grigioni et al. Circulation 2001;103:1759-1764

Time (years)

0 1 2 3 4 5

61%

47%

p<0.001 29%

Survival After MI

MI without MR

100

80

60 ERO 1-19

ERO ≥20

Deja et al. Circulation 2012

p<0.001

0

200

400

600

800

1 2 3 4 5 6 7 8

Ischemic Cardiomyopathy 80

0

Time (years)

0

60

40

20

Mort

alit

y (

perc

ent)

1 2 3 4 5 6

p<0.001

55%

47%

30%

Deja et al. Circulation 2012;125:2639-2648

No MR

Mild MR

Mod-Severe MR

Prevalence of MR in Patients with LV Dysfunction

Prevalence

N MR

Yiu et al Circulation 2000 128 63%

Grigioni et al Circulation 2001 303 64%

Koelling et al Am Heart J 2002 1436 49%

Trichon et al Am J Cardiol 2003 2057 56%

Robbins et al Am J Cardiol 2003 221 59%

Cleland et al N Engl J Med 2004 605 50%

Grayburn et al J Am Coll Cardiol 2005 336 77%

Bursi et al Circulation 2005 303 50%

Acker et al J Thorac CV Surg 2006 300 66%

Di Mauro et al Ann Thorac Surg 2006 239 75%

Rossi et al Heart 2011 1300 74%

Deja et al Circulation 2012 599 63%

Onishi et al Circ Heart Fail 2013 277 48%

Patients with moderate to severe MR *

*

*

*

Secondary mitral regurgitation:

…a marker of a sicker LV

- or -

…a contributor to a sicker LV?

Secondary mitral regurgitation:

…a marker of a sicker LV

- or -

…a therapeutic target?

Therapies that produce beneficial

reverse remodeling also reduce

severity of functional MR


can be repaired.

But should it be repaired?

… or replaced?

Unlike repair of myxomatous MR,

repair of secondary MR

is often not durable

0

5

10

15

20

25

30

1 2 3 4 5 6 7 8

30

20

15

10

5

0

De

ath

(%

)

Recurrent MR at 12 months

MV repair: 33%

MV replacement: 2% 0 3 6 9 12

Time (months)

Acker et al, N Engl J Med 2014;370:23-32

MV replacement (n=125)

MV repair (n=126)

p=0.45 HR=0.79 (95% CI 0.72,1.47)

25

0

10

20

30

40

50

60

70

80

90

100

0

10

20

30

40

50

60

70

80

90

100100

80

60

40

20

0 LV

En

d-S

ysto

lic V

olu

me In

de

x (

mL

/m2)

LV End-Systolic Volume Index

MV

replacement

MV

repair

MV

repair

MV

replacement

Preop 12 months

Recurrent

MR

No recurrent

MR

p=0.18 p=0.001

Acker et al, N Engl J Med 2014;370:23-32

66 61 61 56 64 47

0

10

20

30

40

1 2 3 4 5 8 Time (months)

Goldstein et al, N Engl J Med 2016;374:344-353

40

30

20

10

0

De

ath

(%

)

0 6 12 18 24

MV replacement (n=125)

MV repair (n=126)

HR=0.79 (95% CI 0.46,1.35) p=0.39

0

100

200

300

400

500

600

700

86 87

0

100

200

300

400

500

600

700

86 87

0

100

200

300

400

500

600

700

86 87

0

100

200

300

400

500

600

700

86 87

70

60

50

40

30

20

10

0

Pe

rce

nt o

f P

atie

nts

Recurrent

MR

Death

No MR

Repair Repair Repair Repair Replace Replace Replace Replace

30 days 6 months 12 months 24 months

30% 38% 45% 46%

5%

9% 12%

Death after

MR

Indications for mitral valve surgery:

• Severe MR, persistent symptoms despite optimal medical therapy, including CRT

class IIb

• Patients with severe MR undergoing CABG or AVR

class IIa


class I

• Patients with moderate MR undergoing CABG or AVR

class IIb

Guideline-directed medical

therapy for heart failure,

including CRT

Average hospital mortality: 8.8%

• Low volume centers: 13.0%

• High volume centers: 6.0%

Data from national Medicare database 1994-1999

684 hospitals

142,488 AVRs

Medicare data

0

2

4

6

8

10

12

14

16

86 87 88 90Age Group (years)

16

0

Pre

vale

nce (

perc

ent)

20-34

10

8

45-54 55-64 65-79 35-44 ≥80

4

Men

Women

6

2

14

12

Prevalence of Heart Failure

United States

Source: NHANES, CDC, and American Heart Association




Data from national Medicare database 1994-1999

684 hospitals

142,488 AVRs

Medicare data

0

2

4

6

8

10

12

86 87 88 90Age Group (years)

12

0 50-59

Atrial Fibrillation: Prevalence with Aging

The ATRIA Study

10

8

Go et al, JAMA 2001;285:2370-2375

65-69 75-79 80-84 60-64 70-74 ≥85

4

Men

Women

6

2

n=17,974

Pre

vale

nce (

perc

ent)

0

10

20

30

40

50

60

70

80

90

100

86 87

0

10

20

30

40

50

60

70

80

90

100

86 87

100

80

60

40

20

0

Pe

rce

nt o

f P

atie

nts

Recurrent

AF

Recurrent

AF

Sinus

rhythm

Sinus

rhythm

Baseline Follow-up p=0.005 p=0.72

Severe 36% 29%

71% 64%

Moderate

Mild

18%

18%

64%

19%

19%

57%

5%

Trace/none

Lancet 2006;368:1005-1011

0

1

2

3

4

5

6

7

8

9

10

1 2 3

Perc

ent

Nkomo et al, Lancet 2006;368:1005-1011

7.3

9.6

2

4

8

10

0

Olmstead County (n=16,501)

<45 45-54 55-64 65-74 ≥75

Age

ARIC, CHS, CARDIA (n=11,911)

28,412 subjects

6

Moderate-Severe Mitral Valve Disease

Lancet 2006;368:1005-1011

0

1

2

3

4

5

6

1 2 3

Nkomo et al, Lancet 2006;368:1005-1011

6.0

4.4

4

6

0

Olmstead County (n=16,501)

<45 45-54 55-64 65-74 ≥75

Age

ARIC, CHS, CARDIA (n=11,911)

28,412 subjects

Perc

ent

5

3

1

2

Moderate-Severe Aortic Valve Disease

Aortic Stenosis

Age >60

All patients

Men

Roberts and Ko, Circulation

2005;111:920-925

47% 51%

from Otto and Bonow, Valvular Heart Disease

Braunwald’s Heart Disease, 10th ed, 2014

Stages of Aortic Stenosis

Stage Definition

A Risk of valve disease

B Mild - moderate asymptomatic disease

C Severe valve disease but asymptomatic

C1: Normal LV function

C2: Depressed LV function

D Severe, symptomatic valve disease

D1: High gradient AS

D2: Low gradient, LV dysfunction

D3: Low gradient, normal LV function

BAV, RHD, CVD risk

… the grave prognosis that appears to

accompany the onset of certain symptoms

Ross and Braunwald, Am J Circulation 1968;38:V-61

Ross and Braunwald, Am J Circulation 1968;38:V-61

Circ Cardiovasc Qual Outcomes 2009;2:533-539

0

20

40

60

80

100

0 1 2 3 4

Surv

ival (p

erc

ent)

40

20

0

Bach et al, Circ Cardiovasc Qual Outcomes 2009;2:533-539

0 6 12 18 24 30 36

47%

Time (months)

Aortic Stenosis Survival of Symptomatic Patients

60

80

100

Indications for AVR

• Symptomatic patients with severe AS

Aortic Stenosis

class I

Management challenges:

• The asymptomatic patient with severe AS

• Low-flow, low gradient severe AS

• Indications for TAVR

Aortic Stenosis

Aortic stenosis

Indications for valve replacement

Exercise test results:

• Symptoms

• Hypotension

class I

class IIa

Should asymptomatic patients

with severe AS undergo AVR?

…when they are really asymptomatic?

Aortic Stenosis

84 year old man with severe AS

• Watchful waiting?

• More data (more testing)?

• Aortic valve replacement?




Medicare data

0

20

40

60

80

100

0 1 2 3 4 5

Event-

Fre

e S

urv

ival (%

) 100

80

60

40

20

0 0 1 2 3 4 5

Natural History of Severe Asymptomatic AS

Time (years)

Otto et al. Circulation 1997;95:2262-2270

Rosenhek et al. N Engl J Med 2000;343:611-617

Pellikka et al. Circulation 2005;111:3290-2395

Stewart et al. Eur Heart J 2010;31:2216-2222

Pellikka

Otto

Stewart Rosenhek

Vmax > 4.0 m/s




Medicare data

0

20

40

60

80

100

0 1 2 3 4 5

Event-

Fre

e S

urv

ival (%

) 100

80

60

40

20

0 0 1 2 3 4 5


Time (years)

Rosenhek et al. N Engl J Med 2000;343:611-617

Moderate or severe calcification

No or mild calcification

n=128

p<0.001




Medicare data

0

20

40

60

80

100

0 1 2 3 4 5

Event-

Fre

e S

urv

ival (%

) 100

80

60

40

20

0 0 1 2 3 4 5


Time (years)

Vmax 5.0 – 5.5 m/s

Vmax >5.5 m/s

Vmax 4.0 – 5.0 m/s

Rosenhek et al. Circulation 2010;121:151-156

n=198

p<0.001





What is the risk of death while

waiting for symptoms to trigger AVR?

Aortic Stenosis




Medicare data

0

20

40

60

80

100

0 1 2 3 4 5

Surv

ival (%

) 100

80

60

40

20

0 0 1 2 3 4 5


Time (years)

Pai et al. Ann Thorac Surg 2006;82:116-122

Kang et al. Circulation 2010;121:1502-1509

Nistri et al. Am J Cardiol 2012;109;718-723

Taniguchi et al. J Am Coll Cardiol 2105;66:2827-2838

Pai

Kang

Nistri

Taniguchi




Medicare data

0

20

40

60

80

100

0 1 2 3 4 5

Surv

ival (%

) 100

80

60

40

20

0 0 1 2 3 4 5

Time (years)

Conservative (n=291)

AVR (n=291)

Taniguchi et al. J Am Coll Cardiol 2105;66:2827-2838

85%

74% Taniguchi

31% of patients who developed

symptoms did not have AVR

17 deaths


class IIb

class IIa

Aortic stenosis

Indications for valve replacement

in asymptomatic patients:

• Very severe AS:

Vmax ≥5 m/s

• Rapid progression and low

surgical risk

Aortic stenosis

The ACC/AHA guidelines have

lowered the threshold for surgery

in asymptomatic patients with AS

• Severity of AS

• Severity of calcification

• Left ventricular function

• Exercise response

• BNP?

Aortic stenosis

…but there needs to be

renewed emphasis on the

class I indications for

surgery in symptomatic

patients with severe AS

The ACC/AHA guidelines have

lowered the threshold for surgery

in asymptomatic patients with AS

Aortic stenosis





from Pibarot and Dumesnill, J Am Coll Cardiol 2012:60:1845-1853

Diastole

Systole

Normal Flow

High Gradient

Normal LV Function

Low Flow

Low Gradient

LV Dysfunction

Low Flow

Low Gradient

Normal LV Function

Dobutamine

echocardiography

• Valve calcification

• Myocardial strain

• Myocardial fibrosis

• Clinical skillset

Clavel et al, J Am Coll Cardiol

2013;62:2239-2238

Ozkan et al, Nat Review Cardiol

2011;8:494-501

Herrmann et al, J Am Coll Cardiol

2011;58:402-412

class IIa

Low Flow, Low Gradient Aortic Stenosis

Indications for valve replacement:

• Normal EF, if clinical,

hemodynamic and anatomic

data support severe AS

Aortic stenosis





Indications for TAVR vs surgical AVR:

class I

class IIa

Intervention for Severe AS

• Evaluation by a Heart Team

• Surgical AVR for patients at

low or intermediate risk

• TAVR for patients with

prohibitive surgical risk and

life expectancy >12 months

class I

class I

• TAVR alternative for patients

at high surgical risk

Indications for TAVR vs surgical AVR:

class I

class IIa

Intervention for Severe AS

• Evaluation by a Heart Team

• Surgical AVR for patients at

low or intermediate risk

• TAVR for patients with

prohibitive surgical risk and

life expectancy >12 months

class I

class I

• TAVR alternative for patients

at high surgical risk

?

? class I?

TAVR as alternative?

0

20

40

60

80

100

120

140

160

0

20

40

60

80

100

120

140

160

0

20

40

60

80

100

120

140

160

16

14

12

10

8

6

4

2

0

30-D

ay M

ort

alit

y (

pe

rce

nt)

High Risk Intermediate Risk Low Risk

Thourani et al Ann Thorac Surg 2015;99:55-61

1.7

Observed

Predicted

AVR mortality STS Database

n=141,905

Low Risk

TAVR mortality Clinical Trials

Predicted

Observed

5.3

2.5

NOTION

n=3532

Surgical AVR

1.7

12.9

0

20

40

60

80

100

120

140

160

11.8

3.4

8.6

2.2

7.3

3.3

5.2

2.9 2.1

6.5

4.5

30-D

ay M

ort

alit

y (

pe

rce

nt)

16

10

12

8

6

4

0

13.7

5.5 5.8

14

2

PARTNER A PARTNER II

S3 High Risk

CoreValve

High Risk

PARTNER II

S3 Intermed Risk

CoreValve

Intermed Risk

High Risk Intermediate Risk

PARTNER IIa

5.2

1.1

5.8

3.9

4.1

Barreto-Filho et al, JAMA 2013;210:2078-2085

Aortic Valve Replacement Hospital Mortality

Medicare 1999-2011

0

1

2

3

4

5

6

7

8

9

10

0 1 2 3 4 5

30

Da

y A

VR

Mort

alit

y (

perc

en

t)

8

10

6

4

2

0 1999 2001 2003 2005 2007 2009 2011

7.6%

4.2%

Year

Medicare 1999-2011

N=24,900 N=33,441

Barreto-Filho et al, JAMA 2013;210:2078-2085

Aortic Valve Replacement Hospital Mortality

Medicare 1999-2011

0

1

2

3

4

5

6

7

8

9

10

11

12

13

14

0 1 2 3 4 5

30

Da

y A

VR

Mort

alit

y (

perc

en

t)

8

14

6

4

2

0 1999 2001 2003 2005 2007 2009 2011

5.9%

12.3%

Year

5.8%

3.3%

12

10

Age 65-74

Age 75-84

Age ≥85

Medicare 1999-2011

TAVR Now

• TAVR has been truly transformative

• Surgical AVR remains the standard with proven

durability and safety for most patients

• TAVR provides treatment options for patients

who previously had no options other than a

predictably very poor short term outcome

• TAVR is an alternative to SAVR in patients at

high surgical risk

• The threshold for TAVR is declining in clinical

trials, registries and clinical practice

• All patients want this

TAVR in the Future

• Judgment of the Heart Team remains essential

in patient selection for TAVR

• Appropriate use criteria and performance

measures are needed to define quality

• Guidelines will need to adapt to the rapidly

evolving TAVR evidence base

TAVR in intermediate and low risk surgical patients

• Availability of TAVR is likely to inform new

indications for valve replacement

Moderate AS in primary cardiomyopathy

Asymptomatic severe AS?

• •

Aortic stenosis is a simple mechanical fault

which, if severe enough, imposes a heavy

burden on the left ventricle and sooner or

later overcomes it.

Wood P, Am J Cardiol 1958;1:553-571

management of valvular heart disease 2016 - ilacc.org heart disease 2016 . evidence-based...

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