Bon Secours Heart Valve Center

Virginia’s leader for the management and treatment of valvular heart disease

Dr Scott Lim joins Bon Secours H&VI

Mitral Valve Disease

Mitral Regurgitation (MR)

MR occurs when the mitral valve fails to close completely causing blood flow to flow backward

Mayo Clinic (www.mayoclinic.com)

Symptoms may include: • Shortness of breath • Heart palpitations • Fatigue • Lightheadedness • Cough • Swollen feet or ankles • Excessive urination

Mitral Regurgitation Etiologies Degenerative MR

– Also known as primary or organic MR – Usually caused by an anatomic

defect of one or more structures comprising the mitral valve apparatus—the annulus, the leaflets, the chordae tendineae, and the papillary muscles

Normal Mitral Valve

Degenerative MR: Prolapse

Degenerative MR: Flail

Functional MR

See Important Safety information Referenced Within

Functional MR – Also known as secondary MR – Results from left ventricular (LV)

dysfunction and dilation, which causes otherwise normal valve components to fail and results in MR

Mitral Valve Disease is Commonand Increases with Age

Mitral regurgitation (MR) is the most common type of heart valve insufficiency in the US1,2

1. Heart Disease and Stroke Statistics 2010 Update: A Report From the American Heart Association. Circulation. 2010;121:e46-e215. 2. Nkomo et al. Burden of Valvular Heart Diseases: A Population-based Study, Lancet, 2006; 368: 1005-11.

12

Prevalence of Valvular Heart Disease by Age

Prevalence increases from 0.5% for 18-44

year olds to 9.3% for ≥75 year olds

(p<.0001)

See Important Safety information Referenced Within

MR Progresses to Heart Failure

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 2 Grigioni F, et al. Outcomes in mitral regurgitation due to flail leaflets a multicenter European study. JACC Cardiovasc Imaging. 2008 Mar;1(2):133-41 3 Enriquez-Sarano M, et al. Quantitative determinants of the outcome of asymptomatic mitral regurgitation. N Engl J Med. 2005 Mar 3;352(9):875-83

MR initiates a cascade of events progressing to heart failure, then death, if untreated2,3

Increasing Mitral Regurgitation

Increase Load/Stress

Muscle Damage/Loss

Dysfunctionof Left Ventricle

Dilation ofLeft Ventricle

1 year mortality

up to 57%1

Heart Failure and MR are an Economic Burden

• Estimated annual cost of heart failure is $39.2 billion1

• Majority of treatment costs are due to hospital care1

• Hospitalization following discharge from heart failure admission is high (25% -50% at 30 days)2

Distribution of costs for heart failure treatment in the USA1

Physician, 7%

Home Health Care, 9%Medication, 9%

Nursing Home 13%Hospital Care, 60%

Annual cost of heart failure places a large burden on health care budgets in U.S.

Moderate or greater MR is estimated to occur in 59% patients with heart failure, with the number increasing to 74% in heart failure patients3

1. Braunschweig et al. Europace 2011 2. O’Conner C, et al. J Am Coll Cardiol, 2010; 56:369-371 3. Robbins, et al. Am J Cardiol. 2003 Feb 1;91(3):360-2

See Important Safety information Referenced Within

Severe MR Leads to Increased Hospital Admissions and Lower Survival Rates

0%

20%

40%

60%

80%

100%

0 1 2 3 4 5

East West North

Surv

ival

Pro

babi

lity

No MRMild MR (1+ or 2+)Mod/sev MR (3+ or 4+)

Years

P= 0.0001

Survival of Heart Failure Patients with MR by Degree of MR Adjusted for demographics and clinical variables at baseline

Significantly lower survival rates experienced by patients with moderate to severe MR1

Significantly higher hospital admissions for HF experienced by patients with moderate to severe MR2

HF

Re-

Hos

pit

aliz

atio

n R

ate

(#

ev

ents

/ #

pa

tient

s)

0

4.8

9.5

14.3

19

No/Mild MR Moderate/Severe MR

18.8

10.5

P= 0.021

79% Higher HF

Readmission Rate

Through follow-up ~ 7 yrs (N=218 cases matched 1:1)

1. Trichon BH et al. Am J Card. 2003,91:538-432. Markwick et al. Prognostic Implications of Moderate and Severe Mitral Regurgitation in Contemporary Clinical Care. TCT 2012

A Largely Untreated Patient Population

Total MR Patients1,2

Eligible for Treatment3,4 (MR Grade ≥3+)

4,100,000

1,700,000

Annual MV Surgery5

Annual Incidence3 (MR Grade ≥3+)

250,000

30,000Only 2% Treated Surgically

14% Newly Diagnosed Each Year

1,670,000Untreated Large and Growing Clinical Unmet Need

1. US Census Bureau. Statistical Abstract of the US: 2006, Table 12.2. Nkomo et al. Burden of Valvular Heart Diseases: A Population-based Study, Lancet, 2006; 368: 1005-11.3. Patel et al. Mitral Regurgitation in Patients with Advanced Systolic Heart Failure, J of Cardiac Failure, 2004.4. ACC/AHA 2008 Guidelines for the Management of Patients with Valvular Heart Disease, Circulation: 20085. Gammie, J et al, Trends in Mitral Valve Surgery in the United States: Results from the STS Adult Cardiac Database, Annals of Thoracic Surgery 2010.

Mitral Regurgitation 2009 U.S. Prevalence

Traditional or Open Heart Surgery

• Restricted from driving for one month

• Limited physical activities up to six months.

Minimally Invasive Surgery

• smaller incision, approximately 5 cm

• Without cutting the breastbone

• Return to driving in one week

• Return to normal activities after one month.

Robotic Mitral Valve Surgery

• Small 2 cm incision, between the ribs, and four 1 cm instrument ports

• No driving restrictions

• Return to normal activities within a week or two

Repair vs. Replacement

Advantages of Repair

• Better long-term survival

• Improved lifestyle

• Improved heart function and maintain heart structure

• Better valve durability

• Lower risk of stroke and infection (endocarditis)

• Decreased need for blood thinners (anticoagulation)

Bon Secours Heart Valve Center

99%Repair Success Rate

Mitral referral Criteria

Moderate to Severe MR (3-4+)

• Supporting Criteria

• LVEF < 60%

• LVESD ≥ 40mmHg

• PASP ≥ 50mmHg

• Vena Contracta ≥ 0.7 cm

• Regurgitant Volume ≥ 30 ml

• Regurgitant Fraction ≥ 50%

• ERO ≥ 0.40 cm2

• Moderate to severe LA enlargement

Mitral valve referral criteria

• Moderate to severe MR (3-4+)

High-risk MR Patients are Not Surgical Candidates

1.U.S. Census Bureau, Statistical Abstract of the U.S. 2.Nkomo et al. Burden of Valvular Heart Diseases: A Population-based Study, Lancet, 2006; 368: 1005-11. 3.Patel, et al. Mitral Regurgitation in Patients with Advanced Systolic Heart Failure, J of Cardiac Failure, 2004. 4.Rankin, et al, J of Thoracic and Cardiovascular Surgery, March 2006 5.Nishimura RA, Otto CM, Bonow RO, Carabello BA, Erwin JP III, Guyton RA, O’Gara PT, Ruiz CE, Skubas NJ, Sorajja P. Sundt TM III, Thomas JD, 2014 AHA/ACC Guideline for the Management of Patients with Valvular Heart Disease, Journal of the American College of Cardiology (2014, doi; 10.1016/j.jacc.2014.02.536

* Note: High-Risk Patients are defined as any patient with an EF<35% or an age of 75+.

49% High-Risk Patients*,1-3

(860K)

49% Surgical

Candidates (850K)

2% Surgical Patients (30K)Factors prohibiting

surgery include4: • Impaired LVEF • High operative risk • Multiple comorbidities • Advanced age

Nearly half of MR patients not considered appropriate for mitral valve surgery 4

See Important Safety information Referenced Within

“When patients with VHD are referred for intervention in a timely manner, there is an improved outcome in preservation of ventricular function as well as enhanced survival.”5

MitraClip® Therapy Filling a Treatment Gap

• Medical therapy is limited to symptom management

• MV surgery has been the only option that reliably reduces MR

• A significant gap exists between medical and surgical options

• MitraClip® therapy is a first-in-class, percutaneous option to reduce MR*

Medical Therapy

Less Invasive

Increased MR Reduction

MV SurgeryMitraClip®

*Reference Source: Instructions For Use See important safety information referenced within

INDICATION FOR USE: Prohibitive Risk Primary MR (DMR)

The MitraClip® Clip Delivery System is indicated for the percutaneous reduction of significant symptomatic mitral regurgitation (MR ≥ 3+) due to primary abnormality of the mitral apparatus [degenerative MR] in patients who have been determined to be at prohibitive risk for mitral valve surgery by a heart team, which includes a cardiac surgeon experienced in mitral valve surgery and a cardiologist experienced in mitral valve disease, and in whom existing comorbidities would not preclude the expected benefit from reduction of the mitral regurgitation.

See important safety information referenced within

DMR - Flail

DMR - Prolapse

2014 AHA/ACC Guidelines for the Management of Patients with Valvular Heart Disease

See important safety information referenced within

“Class IIb 3. Transcatheter mitral valve repair may be considered for severely symptomatic patients (NYHA class III to IV) with chronic severe primary MR (stage D) who have favorable anatomy for the repair procedure and a reasonable life expectancy but who have a prohibitive surgical risk because of severe comorbidities and remain severely symptomatic despite optimal GDMT for HF (426). (Level of Evidence: B)

An RCT of percutaneous mitral valve repair using the MitraClip device versus surgical mitral repair was conducted in the United States. The clip was found to be safe but less effective than surgical repair because residual MR was more prevalent in the percutaneous group. However, the clip did reduce severity of MR, improved symptoms, and led to reverse LV remodeling. Percutaneous mitral valve repair should only be considered for patients with chronic primary MR who remain severely symptomatic with NYHA class III to IV HF symptoms despite optimal GDMT for HF and who are considered inoperable.”¹

¹Source: Nishimura RA, Otto CM, Bonow RO, Carabello BA, Erwin JP III, Guyton RA,O’Gara PT, Ruiz CE, Skubas NJ, Sorajja P, Sundt TM III, Thomas JD, 2014 AHA/ACC Guideline for the Management of Patients With Valvular Heart Disease, Journal of the American College of Cardiology (2014), doi: 10.1016/j.jacc.2014.02.536.

Patient Selection Criteria: Prohibitive Risk DMR

For a complete list of patient eligibility criteria, please refer to the MitraClip Clip Delivery System Instructions for Use Reference Source: Instructions For Use See important safety information referenced within

MitraClip® System Overview

MitraClip

MitraClip animation

Improvement In MR with MitraClip® Therapy1

MR Pre-MitraClip® Therapy Baseline*

MR Post-MitraClip ® Therapy 30 Days*

1MitraClip Clip Delivery System Instructions for Use.

*Actual prohibitive-risk DMR patient. Data on file with Abbott Vascular.

See important safety information referenced within

Procedure Imaging:MitraClip

®

Procedure is Guided by Echocardiography

Echocardiography (Primary Imaging)

Fluoroscopy (Secondary Imaging)

Connect With Your MitraClip® Therapy Center

Do you have patients who could benefit from this important treatment option?

Screening for TMVR and referring to MitraClip® therapy could change your patients’ lives.1,2

To find out if TMVR with MitraClip® therapy is an appropriate option for your patients, connect with your local MitraClip® therapy center.

1. MitraClip Clip Delivery System Instructions for Use.2. Lim S, et al. Effectiveness of Transcatheter Mitral Valve Repair for Degenerative Mitral Regurgitation in High Surgical Risk Patients. Presented at: TCT 2012; October 22-26, 2012; Miami, FL.

See important safety information referenced within

MitraClip FDAApproval 2013Based on EVEREST data, the FDA approved the MitraClip for:

Degenerative Mitral Regurgitation

Prohibitive Surgical risk

Risk outweighs benefit of surgery

STS >8%

What about functional MR?

Ischemic Cardiomyopathy

Non-ischemic

Tethering

Annular Dilation

Papillary dysfunction

COAPT Clinical Outcomes Assessment of the MitraClip Percutaneous Therapy for High Surgical Risk Paitents

Prospective randomized multicenter trial for MitraClip treatment of Functional MR

Randomized 1:1 ratio: MitraClip + best medical therapy versus best medical therapy alone

Optimal HF therapy stable for > 30-90 days

Inclusion: 3 - 4+ functional MR (corelab confirmed) LV dysfunction

EF 20-50%; LVESD < 70mm

Aortic Valve Disease

Aortic Stenosis ReferralAortic Stenosis (AS)

• Moderate to severe stenosis

• Supporting Criteria

• Aortic Valve Area < 1.0 cm2

• Aortic Vmax ≥ 4 m/s

• Mean ΔP ≥ 40 mmHg

Aortic SurgicalTraditional or Open Heart Surgery

Open heart patients are restricted from driving for one month and have limited physical activities up to six months.

Minimally Invasive Aortic Valve Surgery

- Mini sternotomy patients are restricted from driving for one month and can return to normal activities within two to three weeks.

- Thoracotomy approach with an incision between the ribs (still needs more)

Over 40 Million People in the US Over the Age of 651

• Aortic stenosis is estimated to be prevalent in up to 7% of the population over the age of 652

• Between 1990 and 2020, the population from 65 – 74 years will increase 74%

• 80% of adults with symptomatic aortic stenosis are male3

Population at Risk for Aortic Stenosis is Increasing

Population: 1960 to 2050 (In Millions)

Elderly

0

20

40

60

80

1960 1970 1980 1990 2000 2010 2020 2030 2040 2050

78.975.2

69.4

53.2

39.434.7

31.125.6

2016.6

Source: US Census Bureau, (US Census, 2010)1

• Shortness of breath

• Angina

• Fatigue

• Syncope or presyncope

• Other

• Rapid or irregular heartbeat

• Palpitations

Symptoms of Aortic Stenosis4

The symptoms of aortic disease are commonly misunderstood by patients as ‘normal’ signs of aging.5 Many patients initially appear asymptomatic, but on closer examination up to 37% exhibit symptoms.6

Sandy Actual TAVR Patient

Pre-Procedure Inoperable

• After the onset of symptoms, patients with severe aortic stenosis have a survival rate as low as 50% at 2 years and 20% at 5 years without aortic valve replacement2

• The PARTNER Trial demonstrated that 50% of inoperable patients died within 1 year without a valve replacement

Severe Aortic Stenosis Is Life Threatening and Progresses Rapidly7

0

8

15

23

30

2830

12

4

23

Worse Prognosis than Many Metastatic Cancers

5-Year Survival (Distant Metastasis)8

Sur

viva

l, %

Breast Cancer

Lung Cancer

Colorectal Cancer

Prostate Cancer

Ovarian Cancer

Severe Inoperable AS*

*Using constant hazard ratio. Data on file, Edwards Lifesciences LLC. Analysis courtesy of Murat Tuczu, MD, Cleveland Clinic

▪ 5 year survival of breast cancer, lung cancer, prostate cancer, ovarian cancer and severe inoperable aortic stenosis

An Under-diagnosed and Under-treated Disease

▪ Studies show at least 40% of severe aortic stenosis (SAS) patients are not treated with an AVR11-17

What Causes Aortic Stenosis in Adults

Age-Related Calcific Aortic

StenosisCongenital

Abnormality

More CommonLess Common

Rheumatic Fever

Images courtesy of John Webb, MD at St. Paul’s Hospital and Renu Virmani, MD at the CVPath Institute

SurgeryLow- to

Moderate-Risk

High Risk Greater Risk

TAVR

Open-Heart Surgery (AVR)

Minimal Incision Valve Surgery(MIVS)

Options for Aortic Valve Replacement

Transcatheter Heart Valve

Surgical Heart Valve

High Risk PatientsDefined by Risk of Mortality > 15%

▪ Aortic valve replacement is intended to relieve the stress on the left ventricle by:

▪Maximizing area

▪Maximizing laminar flow

Immediate Goals of AS Treatment9

Disease Mechanisms and Time Course of Calcific Aortic Stenosis.

Otto CM, Prendergast B. N Engl J Med 2014;371:744-756

Anatomical Changes Associated with Aortic Stenosis.

Otto CM, Prendergast B. N Engl J Med 2014;371:744-756

Mini AVR

7

Landmark PARTNER Trials

High-Risk Patients: Defined by Risk of Mortality ≥ 15%

Inoperable Patients: Defined by Risk of Mortality > 50%

8

Numbers at RiskStandard Rx

179 121 85 62 46 27 17TAVR 179 138 124 110 101 88 70

Absolute Reduction in Mortality at 3 Year in Inoperable Patients

30.7%

50.8%

43.0%

68.0%

54.1%

80.9%

All

Cau

se M

orta

lity

(%)

Months

HR [95% CI] = 0.53 [0.41, 0.68] p (log rank) < 0.0001

20.1%

25.0%

NNT = 5.0 pts

NNT = 4.0 pts

NNT = 3.7 pts

Standard RxTAVR

0%

20%

40%

60%

80%

100%

0 6 12 18 24 30 36

26.8%

9

Reh

ospi

taliz

atio

n (%

)

0%

25%

50%

75%

100%

0.0000 6.0000 12.0000 18.0000 24.0000 30.0000 36.0000

Numbers at RiskStandard Rx

179 86 49 30 19 11 7TAVR 179 115 100 89 77 64 49

Reduction in Repeat Hospitalization in Inoperable Patients

27.0%

53.9%

34.9%

72.5%

42.3%

75.7%

Months

HR [95% CI] = 0.39 [0.28, 0.54] p (log rank) < 0.0001

26.9

37.6%

NNT = 3.7 pts

NNT = 2.7 pts

NNT = 3.0 pts

Standard RxTAVR

Rehospitalization

Days Alive Out of Hospital Median [IQR] TAVR 944 [233-1096]

Standard Rx 368 [147-1096]

p <.0001

33.4%

11

All-

Cau

se M

orta

lity

0%

70%

Months post Randomization0.0000 6.0000 12.0000 18.0000 24.0000 30.0000 36.0000

Numbers at RiskAVR 351 252 236 223 202 174 142TAVR 348 298 261 239 222 187 149Transfemo 244 215 188 174 161 140 108

Edwards SAPIEN All-Cause Mortality Non-Inferior to Surgical AVR in High-Risk Patients at 3 years

HR [95% CI] = 0.93 [0.74, 1.15] p (log rank) = 0.483

26.8%

24.3%

34.6%

33.7%

44.8%

44.2%

AVRTAVRTransfemoral

All-

Cau

se M

orta

lity

0%

70%

Months post Randomization

0.0000 6.0000 12.0000 18.0000 24.0000 30.0000 36.0000