The Changing Epidemiology of Valvular Heart Disease: Implications for Interventional Treatment Alternatives. Martin B. Leon, MD

Transcription

1 The Changing Epidemiology of Valvular Heart Disease: Implications for Interventional Treatment Alternatives Martin B. Leon, MD Columbia University Medical Center Cardiovascular Research Foundation New York City Angioplasty Summit TCT Asia-Pacific 2007 April 25-27, 27, 2007; Seoul, Korea

2 Presenter Disclosure Information for Angioplasty Summit 2007 Martin B. Leon, M.D. Consultant or Advisory Board: Sadra,, Edwards Lifesciences,, GDS Stockholder or other Equity: Sadra,, GDS, Mitralign

3 TVT Epidemiology Roadmap for this lecture What is the prevalence of moderate/severe valvular heart disease,, now and in the future? changing epidemiology? Is there an unmet clinical need in patients with moderate/severe valvular heart, such that interventional therapies (if successful) can expand the treatment armamentarium beyond medical Rx and surgery?

4 Euro Heart Survey on Valvular Heart Disease 92 hospitals from 25 countries 5,001 patients enrolled from April-July, 2001 Eur Heart J. 2003;24:

5 Euro Heart Survey on VHD Single Native Valve Disease % Native VHD 44% 13% 31% 12% 100% 80% 60% 40% 20% 0% AS AR MR MS Other Ischemic Congenital Inflammatory Endocarditis Rheumatic Degenerative Eur Heart J. 2003;24:

6 Euro Heart VHD Survey 30-Day Surgical Mortality STS 2001 UKCSR EHS 2001 Aortic valve replacement no CABG Aortic valve replacement + CABG Mitral valve repair no CABG Mitral valve replacement no CABG Mitral valve repair or replacement + CABG Multiple valve replacement (with or without CABG)

7 Prevalence of Valvular Heart Diseases ,000,000 2,500,000 2,000,000 1,500,000 1,000, ,000 Mitral Regurgitation Aortic Stenosis Severe MR Severe AS Note: CAGR is for ; 2010; Source: Health Research International

8 Valve Procedures by Location , , , , , ,000 80,000 60,000 40,000 20,000 0 Aortic Mitral Other

9 Increasing Prevalence of Valvular Heart Disease in the Elderly Prevalence of moderate or severe valve disease (%) Population-based Studies All valve disease Mitral valve disease Aortic valve disease 0 < > Olmsted County, MN 0 < >75 Nkomo VT at al. Lancet 2006;368:

10 Survival After Detection of Moderate or Severe Valvular Heart Disease Without valve disease With valve disease p< Survival (%) Population-based Studies p< Olmsted County, MN Years Years Nkomo VT at al. Lancet 2006;368:

11 The Potential Population of AS Pts Requiring Treatment 2004 Population AS Prevalence Severe AS Severe AS 50% with Sx ,841, % 41,947 20, ,618, % 27,746 13, ,078, % 58,158 29, ,463, % 86,163 43,081 >75 17,830, % 273, ,701 Total 232,833, , ,708 Based upon the Olmsted County AS prevalence data and US poplulation statistics, the potential AS treatment cohort could exceed 250,000 patients!

12 Projected AVR Procedures (US) # Implants 80,000 70,000 60,000 50,000 40,000 30,000 20,000 10, ,768 72,619 66,980 59,263 61,658 64,

13 MR Demographics: Disease Etiology and Severity Degenerative 20% 30% 50% Moderate 35% Severe 15% 50% Mixed Functional Mild Etiology Severity

14 The presence of moderate or severe Mitral Regurgitation is an independent predictor of poor peri-procedural procedural and late clinical outcomes!!! In every patient population studied Pts with CHF Pts with CAD Pts undergoing PCI Pts undergoing CABG

15 Degenerative Mitral Valve Disease 2 1 Mis-aligned and thickened leaflets allows backflow of blood into the left atrium Surgical Leaflet Repair: Excellent Outcomes Limited to Centers of Excellence Patients are typically referred for surgery when MR grade reaches 3-4+, the ventricle size has increased, functional status has been impaired and they have an acceptable surgical risk.

16 Degenerative Mitral Valve Disease? an underserved population Mitral Valve Prolapse Mitral Valve Prolapse Symptomatic Repairable Valves Patients Suitable for Surgery (Moderate-Severe & Symptomatic) Annual Procedures Surgical or Percutaneous? M 3.0 M 2.7 M 270 K 25 K 2006 U.S. 2% of US Population 50% of MVP Prevalence 90% of valves are amenable to repair 10-15% 15% of MVP are suitable for surgery Annual MVP procedures (incidence) Would a lesser-invasive transcatheter approach make a difference?

17 Functional Mitral Valve Disease MR caused by ischemic disease or cardiomyopathy Regurgitant mitral valve MR begets MR Enlargement of the left ventricle leads to dilation of the mitral annulus and MR Left atrial enlargement Left ventricular dysfunction Reduced efficiency of the heart Increase in ventricle size Patients are generally not considered for surgery and maintained on medical therapy for control of symptoms

18 Functional MR? the tip of the iceberg Congestive Heart Failure CHF with moderate or severe MR 600K 300K 2006 U.S. New cases per year 50% severe MR MV repair procedures (moderate-severe + symptoms) 30 K Functional + degenerative MR Functional MR procedures Surgical or Percutaneous? + 5K 10-20% of MV repairs are for functional MR Would a lesser-invasive transcatheter approach make a difference?

19 TVT Epidemiology Is there really a large pool of patients with mod/severe VHD who are untreated?

20 Severely Symptomatic Patients Require Urgent Attention Survival Percent Valvular Aortic Stenosis In Adults (Average Course) Latent Period (Increasing Obstruction, Myocardial Overload) Onset severe symptoms Angina Syncope Failure Avg. survival Years Age Years Sources: Ross J Jr, Braunwald E. Aortic stenosis. Circulation 1968;38 (Suppl( 1) C.M. Otto. Valve Disease: Timing of Aortic Valve Surgery. Heart Surgical intervention should be performed promptly once even minor symptoms occur

21 Do patients with valvular heart disease receive treatment according to established guidelines? 31.8% did not undergo intervention, despite NYHA class III/IV symptoms

22 Euro Heart Survey: Factors Associated with the Absence of Intervention - Multivariate Analysis - Χ 2 p OR [95% CI] Age >70 years LVEF <60% CHF at admission NYHA class I-II I II vs. III-IV IV [ ] [ ] [ ] [ ] >1 comorbidity [ ] Hosmer-Lemeshow Goodness-of of-fit fit χ 2 =3.2 (df( df=8), p=0.92. c-index: c 0.75 Eur Heart J. 2003;24:

23 Euro Heart Survey Symptomatic MR Isolated MR (n=877) No Severe MR (n=347) Severe MR (n=540) NYHA I-II: 171 No Symptoms n=103 Symptoms n=437 NYHA III-IV: 266 Angina: 168 No Intervention n=226 (52%) Intervention n=211 (48%)

24 Euro Heart Survey Symptomatic AS (elderly( elderly) Aortic Stenosis 75 years N=408 No Severe AS (n=114) Severe AS (n=284) NYHA III:106 No Symptoms N=68 Symptoms N=216 NYHA IV: 36 Angina: 148 No Intervention N=72 (33%) Intervention N=144 (67%) Iung,, B, et al. Eur Heart J 2005;26:

25 Many Severe AS Patients are Not Surgically Treated Severe AS Percent of patients treated Untreated Surgically treated Charlson 2006 US Pellikka 2005 Iung 2003* EU Bouma 1999

26 TVT Epidemiology Are there other important unanswered questions or in need niche VHD populations?

27 Aymptomatic Severe AS Natural History Asymptomatic Severe AS (Jet Velocity >4 m/s) 622 patients 297 develop symptoms 325 remain asymptomatic 207 have surgery 90 no surgery 145 have surgery 180 no surgery 45 died 162 alive 76 died 14 alive 41 died 104 alive 103 died 77 alive Pellikka PA, Sarano ME, Nishimura RA, et al. Circulation ;111: % untreated and 84% die vs. 78% of treated alive

28 Many Presumed Asymptomatic Patients May Not Be Percent of Asymptomatic Patients with Positive Exercise Test Genuinely Asymptomatic Tested Symptomatic Amato 2001 Das 2005 Amato MCM et al. Heart 2001;86: ; 386; Das P et al. European Heart Journal 2005;26:

29 ACC/AHA 2006 Valvular Heart Disease Guidelines: Class I Recommendations for MV Surgery for Chronic MR 1. MV surgery is beneficial for pts with chronic severe MR and NYHA functional class II, III, or IV symptoms in the absence of severe LV dysfunction (LVEF Class <0.30) and/or ESD >55 III: mm. (Level of Evidence: B) Isolated MV surgery 2. MV surgery is beneficial is not indicated for asymptomatic pts with chronic severe MR for and pts mild with to moderate LV dysfunction (LVEF mild 0.30 or moderate , and/or MR ESD 40 mm. (Level of Evidence: B) 3. MV repair is recommended over MVR in the majority of pts who require surgery (Level of Evidence: C) * Bonow RO et al. Circulation and JACC 2006

30 Mitral Regurgitation Natural History of Asymptomatic Chronic MR Cardiac Survival (%) ERO <20 mm 2 ERO mm 2 ERO >40 mm Time (years) Sarano et al. N Engl J Med 2005;352:

31 What are some of the unknowns regarding fringe MR populations? Specific compelling questions High risk pt (usually low LVEF or CHF Sx) ) with functional MR - surgery vs. med Rx? Low risk pt with degenerative or functional MR (mild or moderate) and no Sx,, to alter natural Hx - reduction annuloplasty or leaflet repair vs. med Rx?

32 Why are surgeons so hesitant to operate upon patients with CHF symptoms and moderate or severe functional MR? Increased operative mortality Efficacy (and symptom benefit) + durability of reduction annuloplasty controversial Severity underestimated in the OR (influences of anesthesia and loading conditions)

33 TVT Epidemiology Final Thoughts The population of patients with significant VHD will continue to increase in the future. There is an important group of patients with significant VHD who are currently not being treated with standard surgical therapies for a variety of reasons. There are many untested patient cohorts who might also benefit from earlier VHD therapy (ie( ie. asymp severe AS, early MR )

34 TVT Epidemiology Final Thoughts Undoubtedly, if transcatheter VHD therapy proves to be safe and effective, there are many provocative clinical trial opportunities which can be explored to determine the incremental benefit of a more widely applied lesser-invasive strategy to the treatment of VHD.