Minimally invasive therapies for the mitral valve: How will you incorporate

into your clinical practice?

Guilherme F. Attizzani, MD UH Harrington Heart and Vascular Institute

Interventional Cardiologist/Structural Heart Disease InterventionJohn C. Haugh Valve Fellow

UH Case Medical CenterAssistant Professor of Medicine

Case Western Reserve University School of Medicine

Disclosures

I, Guilherme F. Attizzani, have no conflicts of interest related to this presentation.

Key Aspects – Mitral Regurgitation

Prevalence is agePrevalence is age--dependent, affecting 9.3% dependent, affecting 9.3% of those aged >75 yearsof those aged >75 years

Etiology is primary (i.e., valvular) or Etiology is primary (i.e., valvular) or secondary (i.e., ventricular)secondary (i.e., ventricular)

Excess mortality occurs from medical Excess mortality occurs from medical management and delays in interventionmanagement and delays in intervention

Surgical risk and etiology determine Surgical risk and etiology determine intervention and its timingintervention and its timing

Nkomo et al. Burden of Valvular Heart Diseases: A Population‐based Study, Lancet, 2006; 368: 1005‐11.Suri R et al., JAMA 2013;310:609‐16Nishimura R, et al., J Am Coll Cardiol 2014;63:2438‐88

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

Untreated 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.

A Largely Untreated Patient Population

Mitral Regurgitation 2009 U.S. Prevalence

Flail Mitral Leaflets

Natural History100

80

60

40

20

0

Sur

viva

l %

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

Ling L, et al. N Engl J Med 1996; 335:1417-1423

Hospitalization-free survival decreased with increased MR severity1

100

80

60

40

20

0Hos

pita

lizat

ion-

free

Sur

viva

l (%

)

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

40Tr

ansp

lant

-free

Sur

viva

l (%

)

Days

0 500 1000 1500 2000

Grade IV(46.5 ±6.7%)

Grade III(68.5 ±4.6%)

Secondary Mitral RegurgitationSecondary Mitral RegurgitationIncreased Severity = Increased MorbidityIncreased Severity = Increased Morbidity

Grade II(64.4 ±4.9%)

No MR & Grade I(82.7 ±3.1%)

1. Rossi A, Dini FL, Faggiano P, et al. Heart. 2011;97(20):1675-1680.2. Bursi F, Barbieri A, Grigioni F, et al. Eur J Heart Fail. 2010;12(4):382-388.

Medical Management1,095 pts with severe MR and CHF

55‐‐yr mortality for medically managed = 50%yr mortality for medically managed = 50%

DMRDMR

84%

16%

FMRFMR

36%64%

16%

Goel SS, et al. J Am Coll Cardiol 2014;63:185-90

MitraClip® System

MitraClip® System

MitraClip Experience

EVEREST IEVEREST I Feasibility (n=55)Feasibility (n=55)

EVEREST IIEVEREST II Pivotal Pivotal PrePre--Randomization (n=60)Randomization (n=60) HR Registry (n= 78)HR Registry (n= 78) Randomized Randomized (2:1 Clip to Surgery) (2:1 Clip to Surgery) (n= 279)(n= 279)

Worldwide Commercial Use: Worldwide Commercial Use: >15,000 patients>15,000 patients

REALISMREALISM RegistryRegistryContinued Access (n=965)Continued Access (n=965)

Prohibitive Surgical Risk DMR Cohort (n=127)

Left Ventricular Volumes

Hospitalizations for Heart Failure

Left Ventricular End Diastolic Volume Left Ventricular End Systolic Volume

(N = 69)PairedData (N=69)

0.67

0.18

0.0

0.2

0.4

0.6

0.8

1.0

1 Year Prior… 1 Year Post…

HF Hospitalization Rate pe

r Pa

tien

t Year

73% Reduction

125

109

60

70

80

90

100

110

120

130

140

Baseline 1 Year

Volu

me

mL

‐16 mL

0 ≈

49

46

30

35

40

45

50

55

60

Baseline 1 Year0 ≈

‐3 mL

0

1+

3+

4+

2+Clinically Important Reduction of Mitral Regurgitation

I

II

IVIIIClinically Important Improvement

in NYHA Functional Class

Clinically Important Reduction in the Rate of Hospitalization

for Heart Failure

Clinically Important Reverse LV Remodeling

Lim et al., JACC 2014;64:182-192.

EVEREST II 4‐y FU

Mauri L, et al. JACC 2014

Mitral Regurgitation Improvement

6-min walk distance improvement

Potential for expanded indications

Attizzani GF, JACC Intv. “In Press”

Attizzani GF, JACC Intv. “In Press”

Potential for expanded indications

Attizzani GF, JACC Intv. “In Press”

Potential for expanded indications

May be considered for prohibitive risk patients with significant symptomatic 

primary mitral regurgitation (MR ≥ 3+) and severe symptoms despite GDMT. Risk should be determined by a heart team that includes 

a cardiac surgeon experienced in mitral valve surgery and a cardiologist experienced 

in mitral valve disease (class IIb)

ACC/AHA Guidelines - MitraClip

Nishimura et al., JACC 2014

Take Home Messages

Patients withPatients with MR ≥ 3+ who are considered to be of prohibitive risk for surgery currently have a percutaneous treatment option.

MitraClip procedure is associated with very MitraClip procedure is associated with very low rates of complications and early, low rates of complications and early, sustained improvement in MR, NYHA sustained improvement in MR, NYHA functional class and QOL.functional class and QOL.

Transesophageal echo is a mandatory Transesophageal echo is a mandatory screening exam to check for procedure screening exam to check for procedure suitability.suitability.