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Aortic Stenosis: Tips

for Primary Care and

Newer Treatment

Options Sunil Mankad, MD, FACC, FCCP, FASE

Associate Professor of Medicine

Mayo Clinic College of Medicine

Director, Transesophageal Echocardiography

Associate Director, Cardiology Fellowship

Mayo Clinic, Rochester, MN

mankad.sunil@mayo.edu

@MDMankad

DISCLOSURE: Sunil Mankad

Relevant Financial Relationship(s)

None

Off Label Usage

None

• Canadians: Please divert your course 15 degrees to the South to avoid collision.

• United States: Recommend you divert your course 15 degrees to the North to avoid a collision.

This is a transcript of an actual radio conversation between a US Naval ship and Canadian authorities off the coast of Newfoundland in October, 1995. Radio conversation released by the Chief of Naval Operations 10/10/95

• Canadians: Negative. We insist that you divert your course 15 degrees to the South to avoid a collision.

• United States: This is the Captain of a US Navy Ship. I say again, divert YOUR course.

• Canadians: No. I say again, you divert YOUR course.

• United States: This is the aircraft carrier USS Lincoln, the second largest ship in the United States’ Atlantic Fleet. We are accompanied by three destroyers, three cruisers, and numerous support vessels. I demand that you change your course 15 degrees North! I say again, that’s one five degrees North or counter-measures will be undertaken to ensure the safety of this ship.

• Canadians: This is a lighthouse. Your call.

Photo by Lynn Botterman

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Aortic Valve Disease: Stenosis

• Epidemiology, Pathophysiology, and Natural History of Aortic Stenosis

• Assessment of Severity

• Imaging

• Hemodynamics

• Role of Stress Testing

• Timing of Intervention

• Transcatheter Aortic Valve Replacement (TAVR)

2014 AHA/ACC Guideline for the

Management of Patients With

Valvular Heart Disease

Developed in Collaboration with the American Association for Thoracic Surgery,

American Society of Echocardiography, Society for Cardiovascular Angiography and

Interventions, Society of Cardiovascular Anesthesiologists, and Society of Thoracic

Surgeons

© American College of Cardiology Foundation and American Heart Association

Circulation. 2014 Jun 10;129(23):e521-643

Nishimura RA, Otto CM, Bonow RO, Carabello BA, Erwin JP 3rd, Guyton RA, O'Gara PT, Ruiz

CE, Skubas NJ, Sorajja P, Sundt TM 3rd, Thomas JD; ACC/AHA Task Force Members.

Frequency of Echocardiograms in Asymptomatic Patients With VHD and Normal Left Ventricular Function

Valve Lesion

Stage Aortic Stenosis Aortic

Regurgitation Mitral Stenosis

Mitral

Regurgitation

Progressive

(stage B)

Every 3–5 y

(mild severity

Vmax 2.0–2.9 m/s)

Every 1–2 y

(moderate

severity

Vmax 3.0–3.9 m/s)

Every 3-5 y

(mild severity)

Every 1-2 y

(moderate

severity)

Every 3–5 y

(MVA >1.5 cm2)

Every 3–5 y

(mild severity)

Every 1–2 y

(moderate

severity)

Severe

(stage C)

Every 1 y

(Vmax ≥4 m/s)

Every 1 y

Dilating LV–

more frequent

Every 1–2 y

(MVA 1.0–1.5 cm2)

Every 1 y

(MVA <1 cm2)

Every 6 months

to 1 y

Dilating LV–

more frequent

Circulation. 2014 Jun 10;129(23):e521-643

A Parisian Shoemaker named Carolus Rayger died suddenly (1672)

- reported by Bonetus in 1679 - “Sepulchretum” – aortic valves of “bone”

Aortic Stenosis: Background

• Aortic stenosis (AS) is the 3rd most common cardiovascular disorder in the US, trailing only HTN and CAD

• Most common valvular lesion

• Prevlalence increases with age

• Severe AS affects 3-4% of persons >75 yrs old

• Most common reason for valve replacement

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Normal Aortic Valve A B

L

R

N

N L

R

N = non-coronary cusp; L = left coronary cusp; R = right coronary cusp

Michelena HI, Mankad S, Sarano ME. Atlas of Echocardiography, 2009

• Normal Valve Area = 3 to 4 cm2

Calcific Aortic Stenosis

Michelena HI, Mankad S, Sarano ME. Atlas of Echocardiography, 2009

Causes of Aortic Stenosis

Passik CS, et al: Mayo Clin Proc 62:119, 1987

< 70 years old (n=324) > 71 years old (n=324)

Timing of peak

Single

Component S2

Duration S4

S1 S2 S1

Aortic Stenosis

Distinguishing AS vs HOCM

Image from Healio.com

Risk Factors for Aortic Stenosis • Similar to atherosclerosis

• Hypertension • Hypercholesterolemia • Smoking • Male • Lp(a) • Diabetes

• Autopsy studies have revealed that initial lesion of AS resembles that of coronary artery plaque

• Rajamannan et al (Circulation 2003) showed that calcific aortic valves obtained at time of AVR exhibited dynamic calcification, similar to that of skeletal bone formation

Otto CM. Aortic stenosis: Clinical evaluation and optimal timing of surgery.Cardiology Clinics 1998;16:353.

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Aortic Sclerosis • Aortic sclerosis and aortic stenosis most

likely represent different stages in the same disease process

Olsen MH... Devereaux RB; LIFE substudy. Am J Cardiol 2005;95:132-6.

Aortic Stenosis: Medical Therapy

Recommendations COR LOE

Statin therapy is not indicated for prevention of

hemodynamic progression of AS in patients

with mild-to-moderate calcific valve disease

(stages B to D)

III: No

Benefit A

Nishimura RA et al. Circulation. 2014 Jun 10;129(23):e521-643

Aortic Stenosis: Pathophysiology

• Pressure overload of the LV

• As obstruction progresses, LV adapts in an attempt to keep wall stress normal

• Laplace’s law → LV Hypertrophy • Wall stress = LV systolic pressure x radius/ 2 x wall thickness

• If LV does not hypertrophy adequately to maintain normal wall stress, “afterload mismatch” will occur

• Diastolic function abnormal diastolic stiffness and subsequent LVEDP

• LV performance is subsequently impaired • Decline in LV ejection fraction

Boudoulas H, Gravanis MB: Valvular heart disease. In Gravanis MB: Cardiovascular Disorders: Pathogenesis and Pathophysiology. 1993, p 64.)

Aortic Stenosis LV Pressure Hypertrophy

Long-Axis View

LA

LV

RV

Ao

Courtesy of W. Edwards

Aortic Stenosis: LV Hypertrophy

HITHERTO unsettled problem of the pathologic physiology of the

circulation has been the in vivo estimation of degrees of valvular stenosis.

Because of the essentially fixed nature of the rings of the cardiac valves

when disease, an attempt has been made to apply the hydraulic principles

and formulas of fixed orifices to these stenotic valves.

A

American Heart Journal

Original Communications

HYDRAULIC FORMULA FOR CALCULATION OF

THE AREA OF THE STENOTIC VALVES

R. GORLIN, M.D., AND S.G. GORLIN, M.E.

BOSTON, MASS.

VOL. 41 JANUARY, 1951 No. 1

“in vivo estimation of degrees of

valvular stenosis.”

“……to apply the hydraulic

principles and formulas of fixed

orifices to these stenotic valves.”

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AVA = Forward flow rate

44.3C mean grad

CO ÷ [SEP HR]

44.3C mean grad =

Gorlin formula

Hakki formula

CO

mean grad AVA =

*co-existent regurgitation AVA underestimation

LVOT TVI LVOT area

AV area

=

x

AV TVI

% of Aortic Stenosis Pts Undergoing Invasive Hemodynamics, After Doppler

Exam, Prior to Valve Replacement Mayo Clinic

Roger et al. Mayo Clinic Proc 1996;71:141-149

Early 1980s

95

13 13

98 99

Pt underg

oin

g invasiv

e

hem

odynam

ics (

%)

Year

1990 91 92 93 94 (122) (149) (152) (160) (145)

54

40 35

29 23

0

20

40

60

80

100

Severity of Aortic Stenosis

Echo/Doppler

Parameter

Mild Moderate Severe

Velocity

(meters/sec)

< 3.0 3.0 - 4.0 > 4.0

Mean Gradient

(mmHg)

< 25 25 - 40 > 40

Valve Area (cm2) > 1.5 1.0 - 1.5 < 1.0

Valve Area Index

(cm2/m2)

< 0.6

Aortic Valve Area Equivalents

(cm2)

2.5 1.2 0.95 0.5 0.5

• 622 patients with severe AS

• Peak velocity ≥ 4 m/sec

• Mean Age = 72 ±11 yrs

• Mean FU = 5.4 ± 4.0 yrs

• Sudden death without preceding symptoms occurred in 1% per year of unoperated pts

Circulation 2005;111:3290-3295

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Years No. at risk 397 265 185 128 80 47 25 15 9 6

Survival free of

symptoms (%)

0

20

40

60

80

100

0 1 2 3 4 5 6 7 8 9 10

Survival Free of Symptoms of Severe AS Censored at AV Surgery

Pellikka, Circulation 111:2005: 3290-5

• AS is Progressive

• Average peak velocity increases 0.3 m/sec per year

• Average AVA decreases 0.1 cm2 per year

Otto et al Circulation. 1997;95:2262

Survival in Asymptomatic Severe AS

Su

rviv

al

(%)

Time (yrs) after Dx asymptomatic severe AS

Brown ML, et al J Thorac Cardiovasc Surg 2008

No Symptoms: AVR

Symptoms : AVR

No Symptoms:

ØAVR

Symptoms: ØAVR

n = 622

Kaplan-Meier Survival Curves Comparing Asymptomatic Severe Aortic Stenosis Patients

with and without Aortic Valve Replacement

Cum survival

Pai et al: Ann Thorac Surg 82:2116, 2006

Years

No. at risk 99 87 78 71 64 55 46 35 25 20 11 (AVR)

239 140 104 86 68 57 38 28 18 14 6 (no AVR)

Survival 1 yr 2 yr 5 yr AVR 94% 93% 90% No AVR 67% 56% 38%

P<0.0001

No AVR (n=239)

AVR (n=99)

0.0

0.2

0.4

0.6

0.8

1.0

0 2 4 6 8 10 12

Aortic Stenosis: Timing of Intervention

Recommendations COR LOE AVR is recommended with severe high-gradient

AS who have symptoms by history or on exercise

testing

I B

AVR is recommended for asymptomatic patients

with severe AS and LVEF <50% I B

AVR is indicated for patients with severe AS when

undergoing other cardiac surgery I B

Nishimura RA et al. Circulation. 2014 Jun 10;129(23):e521-643

Aortic Stenosis: Timing of Intervention (cont.) Recommendations COR LOE

AVR is reasonable for asymptomatic patients with

very severe AS (mean gradient ≥ 60 mm Hg)

and low surgical risk

IIa B

AVR is reasonable in symptomatic patients with

low-flow/low-gradient severe AS with reduced

LVEF when a low-dose dobutamine stress study

that shows an aortic velocity 4 m/s (or mean

pressure gradient 40 mm Hg) with a valve area

1.0 cm2 at any dobutamine dose

IIa B

AVR is reasonable in symptomatic patients who

have low-flow/low-gradient severe AS who are

normotensive and have an LVEF ≥ 50% if clinical,

hemodynamic, and anatomic data support valve

obstruction as the most likely cause of symptoms

IIa C

Case

• 82 year old male

• “Asymptomatic” aortic stenosis • Swims ½ hour several times/week

• Slow pace

• Episode of severe dyspnea on 1 occasion

• NYHA functional class I

• HTN, Hyperlipidemia, Glucose intolerance, Glaucoma

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Medications • Allopurinol

• Losartan

• ASA

• Centrum Silver

• Xalatan eye drops

• Flonase

• Rosuvastatin

Labs

• BNP 62 pg/ml

• LDL 41 mg/dl

• Otherwise WNL

EKG

CXR Echocardiogram

• LA volume index 36 cc/m2 (mildly dilated)

• Grade I diastolic dysfunction (impaired relaxation)

• E/e’ 10 (at rest)

• Normal LV mass index

• LV EF 60%

Severe Aortic Stenosis

• Mean Gradient 45 mmHg

• AVA 0.81 cm2

What would you recommend?

1. Yearly follow-up in valve clinic with serial echo

2. Stress test

3. Referral for AVR

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What would you recommend?

1. Yearly follow-up in valve clinic with serial echo

2. Stress test

3. Referral for AVR

Supine Bike Stress Echo

• Patient reached 125 Watts

• Fall in BP

• Pre-peak 178/84 mmHg

• Peak 148/84 mmHg

• Dyspnea, no angina

• Drop in EF

• Baseline – 60%

• Peak – 45%

Supine Bike Echo

Stress

Baseline Catheterization

• No significant CAD

Underwent AVR

Doing well

Am J Cardiol 2009;104:972–977

•No significant complications with stress testing

Sudden Cardiac Death

Rafique et al. Am J Cardiol 2009;104:972–977

• 0/179 patients with normal stress test had SCD

• 9/183 patients with abnormal stress test had SCD

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Aortic Stenosis: Diagnosis and Follow-Up

Recommendations COR LOE

Exercise testing is reasonable to assess

physiological changes with exercise and to confirm

the absence of symptoms in asymptomatic

patients with a calcified aortic valve and an aortic

velocity 4.0 m per second or greater or mean

pressure gradient 40 mm Hg or higher (stage C)

IIa B

Exercise testing should not be performed in

symptomatic patients with AS when the aortic

velocity is 4.0 m per second or greater or mean

pressure gradient is 40 mm Hg or higher (stage D)

III:

Harm B

New Technology

CP1298669-51

Dismal Prognosis in Symptomatic Severe AS Without AVR

Ross J, Braunwald E. Aortic Stenosis. Circulation1968; 38(suppl5);61-7

Aortic Stenosis: Natural History

Schwarz et al Circulation 1982

Carabello and Paulus Lancet 2009

87 Year Old Man with NYHA Class IV Dyspnea

• Physical Exam

•BP 96/67 HR 60

•JVP: elevated

•Carotids: tardus and parvus

•Heart: Single component S2, 3/6 late-peaking SEM, 2/6 HSM at apex

•Lungs: bibasilar crackles

•Ext: 2+ edema

• Past Medical History

•CABG: age 69

•Redo CABG: age 81

•Atrial Fibrillation

•HTN

•Hyperlipidemia

•OSA

•CKD (baseline Cr 2.5)

•Remote tobacco use

•Mild cognitive impairment

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• Meds:

• Statin

• ACE-I

• Beta Blocker

• Diuretic

• Nitrate

• Coumadin

• PPI

• Abnormal Labs:

•Hgb: 11.3 g/dl

•Cr: 2.6 mg/dl

•INR: 2.5

•BNP 1655 pg/ml

87 Year Old Man with NYHA Class IV Dyspnea

EKG

CXR Echocardiogram

• LV Ejection Fraction = 20-25%

• Aortic valve area = 0.58 cm2

• Mean aortic valve gradient = 65 mmHg

• Moderate to Severe MR

• Moderate TR

Aortic Valve – Long-axis View Aortic Valve – Short-axis View

Cardiac Catheterization

• LIMA – LAD patent

• SVG – R-PDA patent

• 100% occluded LAD, LCX, and RCA

• Nothing to revascularize

Summary

• 87 year old man

• Severe AS with Class IV symptoms, LV dysfunction, and multiple co-morbidities

• 2 prior CABG operations

• Creatinine = 2.6 mg/dl

• Options?

• What is the risk of surgery?

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Online STS Risk Calculator

Risk of Mortality = 20.1%

Risk of Morbidity or Mortality = 68.9%

Risk of Long Length of Stay = 39.4%

Risk of Permanent Stroke = 8.1%

Risk of Renal Failure = 31.3%

Assessment of Frailty (Frailty Index Data Collection Form)

To be considered frail, a patient must fail 3 out of 4 categories. Here is the criteria for each category:

• Albumin < 3.5 g/dl = failure in this category

• Grip strength < that recommended grip strength based on BMI

• ADL’s - a total score of 4 or less is failure in this category

• 15 foot/5 meter walk – based on height, walk time greater than or equal to 6-7 seconds (depending on height) is failure in this category

Activities

Points 1 or 0

Independence:

1 Point – No supervision, direction, or

personal assistance

Dependence:

0 Points – With supervision,

direction, personal assistance, or

total care

Bathing ____

1 Point – Bathes self completely or needs help

in bathing only a single part of the body such

as the back, genital area, or disabled extremity

0 Points – Needs help with bathing

more than one part of the body,

getting in or out of the tub/shower

Requires total bathing

Dressing ____

1 Point – Gets clothes from closets and

drawers and puts on clothes and outer

garments complete with fasteners. May have

help tying shoes

0 Points – Needs help dressing self

or needs to be completely dressed

Toileting _____

1 Point – Goes to toilet, gets on and off,

arranges clothes, cleans genital area without

help

0 Points – Needs help transferring

to the toilet, cleaning self or uses

bedpan or commode

Transferring ____

1 Point – Moves in and out of bed or chair

unassisted. Mechanical transfer aids are

acceptable

0 Points – Needs help in moving

from bed to chair or requires

complete transfer

Continence ____

1 Point – Exercises complete self -control over

urination and defecation

0 Points – Is partially or totally

incontinent of bowel or bladder

Feeding ____

1 Point – Gets food from plate into mouth

without help. Preparation of food may be done

by another person.

0 Points – Needs partial or total help

with feeding or requires parenteral

feeding.

Total Points ____

Screening For Vascular Access

Transfemoral Transapical

Transfemoral and Transapical

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Deploying the Valve Rapid Ventricular Pacing

Pre-AVR Post-AVR MG=65 mmHg, AVA=0.5cm2 MG=9mmHg, AVA=2.1cm2

Our Patient

N = 179

N = 358 Inoperable

Standard

Therapy

ASSESSMENT:

Transfemoral

Access

Not In Study

TF TAVR

Primary Endpoint: All-Cause Mortality

Over Length of Trial (Superiority)

Co-Primary Endpoint: Composite of All-Cause Mortality

and Repeat Hospitalization (Superiority)

1:1 Randomization

VS

Yes No

N = 179

TF TAVR AVR

Primary Endpoint: All-Cause Mortality at 1 yr

(Non-inferiority)

TA TAVR AVR VS

VS

N = 248 N = 104 N = 103 N = 244

PARTNER Study Design (High Risk Patients: STS score > 8%)

Symptomatic Severe Aortic Stenosis

ASSESSMENT: High-Risk AVR Candidate

3,105 Total Patients Screened

Total = 1,057 patients

2 Parallel Trials:

Individually Powered

N = 699 High Risk

ASSESSMENT:

Transfemoral

Access

Transapical (TA) Transfemoral (TF)

1:1 Randomization 1:1 Randomization

Yes No

Presented by Michael Mack, MD at ACC 2015

Presented by Michael Mack, MD at ACC 2015

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ACC 2015

ACC 2015

Primary Endpoint: All-Cause Mortality or Disabling Stroke at Two Years

Randomized Patients

n = 2032

Symptomatic Severe Aortic Stenosis

ASSESSMENT by Heart Valve Team

Operable (STS ≥ 4%)

The PARTNER 2A Trial Study Design

TF TAVR

(n = 775)

Surgical AVR

(n = 775) VS. VS.

ASSESSMENT:

Transfemoral Access

Transapical (TA) / TransAortic (TAo) Transfemoral (TF)

1:1 Randomization (n = 482) 1:1 Randomization (n = 1550)

TA/TAo TAVR

(n = 236) Surgical AVR

(n = 246)

Yes No

N Engl J Med 2016; 374:1609-1620

1

1011 918 901 870 842 825 811 801 774

1021 838 812 783 770 747 735 717 695

Number at risk:

TAVR

Surgery

p (log rank) = 0.253

HR [95% CI] = 0.89 [0.73, 1.09]

TAVR

Surgery

0

10

20

30

40

50

19.3%

21.1%

14.5%

16.4%

0 3 6 9 12 15 18 21 24

6.1%

8.0%

Primary Endpoint (ITT) All-Cause Mortality or Disabling Stroke

Months from Procedure

All

-Ca

us

e M

ort

ali

ty o

r D

isa

bli

ng

Str

ok

e (

%)

1

762 717 708 685 663 652 644 634 612

722 636 624 600 591 573 565 555 537

p (log rank) = 0.04

HR: 0.78 [95% CI: 0.61, 0.99]

16.3%

20.0%

0 0 3 6 9 12 15 18 21 24

0

10

20

30

40

50

15.8%

7.5%

11.7%

4.5%

TF Primary Endpoint (AT) All-Cause Mortality or Disabling Stroke

All

-Ca

us

e M

ort

ali

ty o

r D

isa

bli

ng

Str

ok

e (

%)

TF TAVR

TF Surgery

Months from Procedure Number at risk:

TF TAVR

TF Surgery Self Expandable Balloon Expandable

Sapien Valve CoreValve

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2-Year All-cause Mortality

ACC 2014 All Stroke

Conclusions

• Valvular Heart Disease is becoming more prevalent in the elderly

• Important to know when to intervene in severe aortic stenosis

• Novel technologies provide potential answers to treatment gaps in higher risk patients

“Your vision will become clear only when you can look into your own heart -

He who looks outside, dreams

He who looks inside, awakens” Carl Gustav Jung (1875-1961)

“Dream every night as if you will live forever, but live everyday as

if it could be your last”

James Dean

Thank You! mankad.sunil@mayo.edu

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