Greater New York Geriatric Cardiology Consortium: Valve Disease in Older Adults Allan Schwartz, MD Columbia University Medical Center New York Presbyterian Hospital March 2012

Disclosures None

Valvular Disease in Older Adults Prevalence is increasing dramatically as the population ages Predominantly AS and MR Predictably associated with heart failure, arrhythmia and death. Medical treatment has limited effectiveness. Mechanical therapies (surgical and percutaneous) are becoming more “routine” in the elderly.

Valvular Disease in Older Adults Presence of co-morbidities including frailty make patient selection difficult and prediction of overall response to therapy less predictable than in younger patients. Goals of therapy are different in this age group with an emphasis placed on QOL, functionality/independence and palliation of severe symptoms.

Increases in the Very Old U.S. Population Aged 85+ (in millions) Sources of data: U.S. Census Bureau, “65+ in the United States: 2005,” December 2005; U.S. Census Bureau, U.S. Interim Projections by Age, Sex, Race, and Hispanic Origin, 2004.

Nkomo VT et al. Lancet : Valvular Heart Disease Has Increasing Prevalence With Age Olmstead County Population Studies

33.9% 24.8% Lung B et al. Eur Heart J : Type of Valvular Heart Disease 20.2% n=5,001

Valvular Heart Disease Impact Nkomo VT et al. Lancet :

Adapted from Ross and Braunwald, Circulation 1968

Pellikka, P. A. et al. Circulation 2005;111: Survival of asymptomatic patients with AS N=622

Schwartz F et al. Circulation : Medical Rx Group: 19 surgical candidates who refused surgery Mean age: 56 Mean EF: 57% Peak cath gradient: 87mmHg (+/-17mmHg) 20% survival at 2 years ¼ sudden death ¾ CHF/low output Survival of symptomatic patients with AS

Therapeutic Goals Prevent progression to severe AS Improve survival Prevent sudden death Symptom relief Prevent or reverse LV dysfunction/CHF Improve the outcomes of other surgery Minimize treatment related morbidity and mortality

Prevent progression to severe AS Rossebo et al. NEJM,2008,359;13: n = 1873

Current ACC/AHA Guidelines Class I (“should do it”) –Level of Evidence: A None –Level of Evidence: B Symptomatic patients with severe AS –Level of Evidence: C Patients with severe AS undergoing Ao or other heart valve surgery Patients with severe AS and LV systolic dysfunction - EF<50% ACC/AHA VHD 2006 Guidelines: 2008 Update

Current ACC/AHA Guidelines Class I (“should do it”) –Level of Evidence: A None –Level of Evidence: B Symptomatic patients with severe AS –Level of Evidence: C Patients with severe AS undergoing Ao or other heart valve surgery Patients with severe AS and LV systolic dysfunction - EF<50% ACC/AHA VHD 2006 Guidelines: 2008 Update

Aortic Valve Replacement Hospital Mortality n = 108,791 isolated AVR Brown et al. JCTVS 2009;137:82-90

Mortality and Stroke after AVR Brown, et al. JTCVS, January 2009 In current era 37% > 75 yrs

Average hospital mortality: 8.8% Low volume centers: 13.0% Low volume centers: 13.0% High volume centers: 6.0% High volume centers: 6.0% Goodney et al, Ann Thorac Surg 2003;76: Aortic Valve Replacement Hospital Mortality Data from national Medicare database hospitals 142,488 AVRs Medicare data

Aortic Valve Replacement in the Elderly, Contemporary Results n = 1,193 Age >80 Mortality 6.9% CVA 1.7% Langanay, Ann Thorac Surg, 2012, 93, 70-8

Bakaeen et al., Ann Thorac Surg, 2010, 90, Short-Term Outcomes of AVR Stratified by Age

The Oldest Old: Survival of Octogenarians with Severe AS with and without AVR Varadarajan et al. Eur J Cardiothorac Surg. 2006; (5):

Asimakopoulos et al, Circulation 1997;96: AVR/year in Patients >80y Johns Hopkins Octegenarians 1100 pts % 30-d mortality Trends in AVR in the Elderly

Functional status following aortic valve replacement in the elderly Florath I et al. Heart 2005; 91:

But Would They Do It Again? Maillet et al. Arch Gerontology + Geriatrics 2009; 48: In one study, 84 patients age ≥ 80 years of age who underwent AVR +/- CABG for symptomatic AS were queried at least 1 year after surgery whether they would accept being operated on again. 39.3% reported they would not and this was significantly related to loss of autonomy, suspected depression, and cardiac symptoms.

Transcatheter Aortic Valve Replacement (TAVR) Leon, NEJM, 363:17, October 2010

Symptomatic Severe Aortic Stenosis ASSESSMENT: High Risk AVR Candidate 3105 Total Patients Screened ASSESSMENT: High Risk AVR Candidate 3105 Total Patients Screened PARTNER Study Design High Risk TA ASSESSMENT: Transfemoral Access TAVITrans femoralTAVITrans Surgical AVR High Risk TF Primary Endpoint: All Cause Mortality (1 yr) (Non-inferiority) TAVITransapicalTAVITransapical Surgical AVR 1:1 Randomization VS Standard Therapy (usually BAV) Standard Therapy (usually BAV) ASSESSMENT: Transfemoral Access Not In Study TAVITransfemoralTAVITransfemoral Primary Endpoint: All Cause Mortality over length of trial (Superiority) 1:1 Randomization VS Total = 1058 patients 2 Parallel Trials: Individually Powered High Risk n= 700 InoperableInoperable n=358

Patient Characteristics - 1CharacteristicTAVIn=179 Standard Rx n=179 P value Age - yr 83.1 ± ± Male sex (%) STS Score 11.2 ± ± Logistic EuroSCORE26.4 ± ± NYHA I or II (%) III or IV (%) CAD (%) Prior MI (%) Prior CABG (%) Prior PCI (%) Prior BAV (%) CVD (%)

Patient Characteristics - 2Characteristic TAVI TAVI n= 179 Standard Rx Standard Rx n=179 P value PVD (%) COPD Any (%) Any (%) O2 dependent (%) O2 dependent (%) Creatinine >2mg/dL (%) Atrial fibrillation (%) Perm pacemaker (%) Pulmonary HTN (%) Frailty (%) Porcelain aorta (%) Chest wall radiation (%) Chest wall deformity (%) Liver disease (%)

Characteristic TAVR (N = 348) AVR (N = 351) p-value Age (yr)83.6 ± ± Male sex - % STS Score11.8 ± ± Logistic EuroSCORE29.3 ± ± NYHA II - % III or IV - % CAD - % Previous MI - % Prior CV Intervention - % Prior CABG - % Prior PCI - % Prior BAV - % Patient Characteristics (1) Cerebrovascular disease - %

Characteristic TAVR (N = 348) AVR (N = 351) p-value Peripheral vascular disease - % COPD Any 43.4 Oxygen dependent Creatinine > 2mg/dL - % Atrial fibrillation - % Permanent pacemaker - % Pulmonary hypertension - % Frailty - % Porcelain aorta - % Chest wall radiation - % Liver disease - % Patient Characteristics (2)

TAVR Results Smith, NEJM, 364:23, June 2011Leon, NEJM, 363:17, October 2010 High Risk PatientsInoperable Patients

Symptom Improvement After TAVR and Surgery Smith, NEJM, 364:23, June 2011

Quality of Life after Transcatheter Valve Cohen, et al. Slide Presentation, ACC 2011 KCCQ

Primary Endpoint KCCQ Overall Summary 34 MCID = 5 points  = 5.5 P = 0.01  = -2.6 P = NS  = -0.5 P = NS Growth curve analysis; adjusted for baseline MCID = minimum clinically important difference points Cohen et al, TCT 2011

PARTNER Cohort A P = 0.06 P = 0.18 P = 0.03 P = 0.04 TAVI (n=179) Standard Rx (n=179) percent Neurologic Events in PARTNER at 30 days PARTNER Cohort B

At Least 30% of Patients with Severe Symptomatic AS Do Not Undergo AVR Severe Symptomatic Aortic Stenosis Percent of Cardiology Patients Treated 1.Bouma B J et al. To operate or not on elderly patients with aortic stenosis: the decision and its consequences. Heart 1999;82: Iung B et al. A prospective survey of patients with valvular heart disease in Europe: The Euro Heart Survey on Valvular Heart Disease. European Heart Journal 2003;24: (*includes both Aortic Stenosis and Mitral Regurgitation patients) Pellikka, Sarano et al. Outcome of 622 Adults with Asymptomatic, Hemodynamically Significant Aortic Stenosis During Prolonged Follow-Up. Circulation 2005 Charlson E et al. Decision-making and outcomes in severe symptomatic aortic stenosis. J Heart Valve Dis2006;15: No AVR AVR

31.8% did not undergo intervention, despite NYHA class III/IV symptoms Do patients with valvular heart disease receive Do patients with valvular heart disease receive treatment according to established guidelines? 92 hospitals from 25 countries 92 hospitals from 25 countries 5,001 patients from April-July, ,001 patients from April-July, 2001

Decision to operate according to age range Iung, Eur Heart J (December 2005) 26 (24): 2714

Decision to operate according to comorbidities Iung, Eur Heart J (December 2005) 26 (24): 2714

N = 16 STS 11.8 LES 33 N =16 STS 6.3 LES 19 N=52 STS 11.3 LES 31 N=21 STS 10.9 LES 33 Dewey et al, Ann Thorac Surg 2008;86: High Risk Patients Referred for TAVI