Minimally invasive therapies for the mitral valve: How will you incorporate into your clinical practice? Guilherme F.

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 Intervention John C. Haugh Valve Fellow UH Case Medical Center Assistant 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 age-dependent, affecting 9.3% of those aged >75 years Etiology is primary (i.e., valvular) or secondary (i.e., ventricular) Excess mortality occurs from medical management and delays in intervention Surgical risk and etiology determine intervention 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 16 Nishimura R, et al., J Am Coll Cardiol 2014;63:2438 88

A Largely Untreated Patient Population Mitral Regurgitation 2009 U.S. Prevalence Total MR Patients 1,2 4,100,000 Eligible for Treatment 3,4 (MR Grade 3+) Annual Incidence 3 (MR Grade 3+) Annual MV Surgery 5 1,700,000 1,670,000 250,000 30,000 Untreated Large and Growing Clinical Unmet Need 14% Newly Diagnosed Each Year Only 2% Treated Surgically 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: 2008 5. 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.

Flail Mitral Leaflets Natural History 100 Survival % 80 60 40 Class I or II Mortality 4% per year 20 0 Class III or IV P<0.001 0 1 2 3 4 5 6 7 8 9 10 34% per year Years After Diagnosis Ling L, et al. N Engl J Med 1996; 335:1417-1423

Secondary Mitral Regurgitation Increased Severity = Increased Morbidity Hospitalization-free survival decreased with increased MR severity 1 Transplant-free survival decreased with increased MR severity 2 Hospitalization-free Survival (%) 100 80 60 40 20 P<0.01 0 0 1 2 3 4 5 6 7 Years No MR(40%) Mild/mod MR (25%) Severe MR 7%) Transplant-free Survival (%) 100 90 80 70 60 50 Grade IV (46.5 ±6.7%) 40 0 500 1000 1500 2000 Days No MR & Grade I (82.7 ±3.1%) Grade II (64.4 ±4.9%) Grade III (68.5 ±4.6%) 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 Management 1,095 pts with severe MR and CHF FMR DMR 64% 36% 16% 84% 5 yr mortality for medically managed = 50% Goel SS, et al. J Am Coll Cardiol 2014;63:185-90

MitraClip System

MitraClip System

MitraClip Experience EVEREST I Feasibility (n=55) EVEREST II Pivotal Pre-Randomization (n=60) HR Registry (n= 78) Randomized (2:1 Clip to Surgery) (n= 279) REALISM Registry Continued Access (n=965) Worldwide Commercial Use: >15,000 patients

Prohibitive Surgical Risk DMR Cohort (n=127) 0 1+ 2+ Clinically Important Reduction 3+ of Mitral Regurgitation4+ HF Hospitalization Rate per Patient Year 1.0 0.8 Hospitalizations for Heart Failure 73% Reduction 0.67 Clinically 0.6 Important Reduction in the Rate of Hospitalization 0.4 for Heart Failure 0.2 0.18 0.0 1 Year Prior 1 Year Post Left Ventricular End Diastolic Volume Left Ventricular Volumes Left Ventricular End Systolic Volume II III Clinically Important Improvement IV in NYHA Functional Class I Volume ml Paired Data 140 130 120 110 100 90 80 70 60 0 125 109 50 49 Clinically Important Reverse 46 45 Baseline (N = 69) 16 ml LV Remodeling 1 Year 60 55 40 35 30 0 Baseline (N=69) 3 ml 1 Year 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

Potential for expanded indications Attizzani GF, JACC Intv. In Press

Potential for expanded indications Attizzani GF, JACC Intv. In Press

ACC/AHA Guidelines - MitraClip 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) Nishimura et al., JACC 2014

Take Home Messages Patients 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 low rates of complications and early, sustained improvement in MR, NYHA functional class and QOL. Transesophageal echo is a mandatory screening exam to check for procedure suitability.