Outline • Pathogenesis/Natural History • Medical management-Asymptomatic -Symptomatic • Surgical management - TAVI
Pathogenesis • Calcific AS is the most common valve disorder in the western world • 2% of people >65, 3% >75 and 4% >85 have AS (in those with trileaflet valve) • Initially thought to be a passive process of calcium buildup • Evidence now shows that it is an active process-Accumulation of LDL-Inflammation-Calcification Rajamannan NM, et. al. Calcific aortic stenosis: an update. Nat Clin Pract Cardiovasc Med 2007;4:254–262. Stewart BF, et. al. Clinical factors associated with calcific aortic valve disease. Cardiovascular Health Study. J Am Coll Cardiol. 1997; 29: 630-634.
Natural History of AS • Prolonged asymptomatic period until AVA becomes <1/2 normal (3-4cm²) • Average gradient increase is 4-7 mmHg per year • Valve area decreases at an average rate of 0.1cm² per year • Patient’s with jet velocity <3m/sec are unlikely to develop symptoms in next 5 years Otto, CM et. al. Circulation 1997;95(9):2262
Medical ManagementAsymptomatic Patients • Serial echo’s in combination with H&P and assessment of functional status • How often?-Mild AS: Every 3-5 years-Moderate AS: Every 1-2 years-Severe AS: Annually
Medical ManagementAsymptomatic Patients • Hypercholesterolemia/Statin Therapy-A few studies show an association between AS progression and elevated cholesterol-In patients with LDL >130mg/dL, AS progression is more rapid • Does lowering cholesterol slow or prevent progression?
Medical ManagementLipid Trials • SEAS Study1-1873 patients with mean age of 68-Mild to moderate AS-Randomized to simvastatin/ezetimibe vs. placebo-52 month f/u => No difference in rate of hemodynamic progression of AS • SALTIRE Trial²-155 patients with at least moderate calcific AS-Randomized to atorvastatin 80mg vs. placebo-No difference in rate of increase in AoV velocities over 25 month f/u 1. N Engl J Med 2008;359:1343-56. 2. N Engl J Med 2005;352:2389-97.
Medical ManagementHyperlipidemia • Statin therapy for isolated AS does not reduce rates of disease progression • Studies to evaluate potential benefit earlier in disease process have not been performed • Most AS patients have other indications for statin therapy
Medical ManagementHypertension • AS and hypertension often coexist • Afterload is elevated due to increased SBP and valve stenosis (“double-load”) • Axiom of “start low and go slow” especially important in patients with more severe AS
Medical ManagementAntihypertensives • ACE-Inhibitors-Known to have beneficial effects on LV function/remodeling-Little clinical evidence that they benefit patients with AS-Usually tolerated well...watch for hypotension • Diuretics/Nitrates-Use cautiously; preload reduction => Hypotension
Medical ManagementAntihypertensives • Beta-blockers-Bicuspid AS associated with root dilatation which can lead to aneurysm/dissection-AHA/ACC guidelines recommend β-blocker in patients with root >40mm -Patients with low BSA’s should be considered for β-blocker therapy based on aortic size index
Medical ManagementExercise • CO increases with exercise and can therefore exacerbate valve gradient and LVSP • Magnitude of this effect increases with AS severity and exercise intensity • Specific guidelines exist for professional athletes-Even patients with severe AS can bowl and play golf
Medical ManagementSymptomatic Patients • Limited options for medical management once patient becomes symptomatic • Classic triad of symptoms:-Angina-Heart Failure-Syncope Circulation Journal Vol. 75, Jan 2011
Medical ManagementSymptomatic Patients • What about those patients who refuse or are not candidates for surgical correction?-Up to 1/3 of patients are not surgical candidates! • Goals of medical therapy:-treat concurrent conditions-maintain optimal hemodynamics -manage symptoms • Long-term medical therapy for palliation only
Medical ManagementBalloon Valvuloplasty • Performed in those patients who display hemodynamic instability due to AS • Can be used as a bridge to AVR or strictly for palliation of symptoms • Associated with high morbidity and short-lived efficacy-10%-20% rate of stroke, MI and AI-Restenosis and clinical worsening occur within 6-12 months - similar to untreated AS1 J Am Coll Cardiol 1995; 26: 1522
Surgical ManagementThe Beginning • First performed in 1952 by Dr. Charles Hufnagel • Definitive treatment of symptomatic severe AS Hufnagel Artificial Heart Valve in the collection of the National Museum of Health and Medicine
Surgical ManagementModern Day • Multiple options for replacement:-Mechanical-Bioprosthetic-Stented/Stentless-Homografts-Ross (fallen out of favor) • Which is best...
Choice of AVR2006 ACC/AHA/ESC Recommendations • Mechanical Valves-Already have another mechanical valve-<65 without contraindication for anticoagulation (weaker recommendation) • Bioprosthetic Valves-Contraindication or unwilling to take warfarin (any age)-≥65 without risk factors for thromboembolism-<65 in those who make an informed decision
Choice of AVRBioprosthetic • Concerns about bioprosthetic AVR durability and long-term mortality in patients <65 -Veterans Affairs Trial 1 • Subsequent study showed that long-term mortality was not higher in <60 year olds with initial bioprosthetic AVR² • Patient preference and likelihood of repeat surgery 1.J Am Coll Cardiol 2000; 36:1152 2.Circulation 2007; 116: I-294-I-300
AS TreatmentPresent and Future • TAVI first performed in France in 2002 • Increased use throughout the world in patients who are not candidates for surgical AVR • Recently approved for use in the US
TAVICoreValve ReValving System • Manufactured by Medtronic • Self-expandable, trilevel frame of nitinol with porcine pericardium valve • Anchored within the annulus but function is supra-annular
CoreValve SystemClinical Data • Randomized trial comparing CoreValve to surgical replacement is ongoing • Most common complication is need for PPM (10%-15%) Spaccarotella, C et.al. Circulation Journal Vol.75;Jan 2001
TAVIEdwards SAPIEN • Edwards Lifesciences LLC • Balloon-expandable stainless steel frame with equine pericardium valve • Anchoring and function are both intra-annular
Edwards SAPIENClinical Data • SOURCE Registry-463 transfemoral and 575 transapical patients-Overall all-cause mortality was 8.3% at 30 days Transfemoral: 6.3% Transapical: 10.3%-Overall stroke rate of 2.5%; similar in both groups Schymik, G et. al. Circ 2010; 122: 62-69
AS TreatmentPARTNER • Placement of Aortic Transcatheter Valves-Multicenter, randomized trial comparing TAVI with standard therapy in patients with severe AS-Divided into two cohorts: 1) STS of ≥10% but still considered surgical candidates 2) Not surgical candidates due to probability of death or serious irreversible condition of 50% 30 days post-OP • PARTNER reported results of those not deemed surgical candidates
AS TreatmentPARTNER • 3105 patients screened, 358 enrolled from 21 sites (17 in the US) • Followed for at least 1 year (median 1.6; max 2.8) • Primary endpoint was all cause mortality over the trial duration
PARTNEROutcomes • TAVI Group-Median time to TAVI - 6 days-2 deaths, 3 major strokes, 1 valve embolization during procedure or in 1st 24 hours-11/173 died within 30 days • Standard Therapy Group-150/185 underwent balloon valvuloplasty-12 underwent surgical AVR
PARTNERPrimary Endpoint • All cause mortality at 30 days - 5% in TAVI - 2.8% in SMT 20% Reduction in mortality
PARTNERSecondary Endpoints • Increased major bleeding and major vascular complications with TAVI • Greater improvement in symptoms with TAVI-Improvement in 6 minute walk test with TAVI-No change in standard therapy group • Echo evaluation-Mod or severe paravalvular regurg in ~11% of TAVI patients at one year-Mod or severe transvalvular regurg in 1.3 %
“PARTing” Shots • Standard medical therapy did not alter the natural history of severe AS-84% received balloon valvuloplasty • TAVI superior to standard therapy with regard to all cause mortality (1° Endpoint) • More neurologic events in TAVI group • No evidence of valve deterioration one year post-implantation
Let’s Review... • AS is the most common heart valve disease in the industrialized world • No effective long-term medical therapies • AVR is the only therapy that offers prolonged morbidity and mortality benefits • TAVI is a safe alternative in those who are not surgical candidates