Aortic Valve Stenosis and CAD

Transcription

1 EUROECHO 14, Copenhagen 2010 Aortic Valve Stenosis and CAD Aleksandar N. Neskovic Clinical Hospital Center Zemun Belgrade University School of Medicine

2 Aortic Stenosis and CAD Important facts Links AS/CAD o risk factors o pathogenesis o statins Management

3 AS: Important Facts The most prevalent of all valvular diseases in developed countries Manifestation of aging: more prevalent as the average age of the population increases

4 Prevalence of Degenerative AoV Disease by Age Frank AS ~ 2 % 19 7 Stritzke J, et al. KORA/MONICA Survey, EHJ 2009

5 AS: Important facts (cont d) Any calcific AoV disease is associated with increased mortality

6 Calcific AoV Disease Aortic sclerosis stenosis Thickening or calcification of the AoV No significant obstruction of flow (< m/s)

7 AoV Sclerosis is Associated with Increased Risk of CVS Death and MI in the Elderly without CAD Echo in 5621 subjects, >65 yrs Population based prospective F/U 5 yrs Relative Risk* (95% Confidence Interval) CVS death 1.52 ( ) Myocardial infarction 1.40 ( ) * Adjusted for age, sex, and associated baseline factors Otto CM, et al. NEJM 1999

8 AS: Important facts (cont d) Any calcific AoV disease is associated with increased mortality If untreated, symptomatic severe diseases is universally fatal!

9 AS: Natural History Ross J Jr, Braunwald E. Aortic stenosis. Circ 1968

10 Angina in AS Exertional angina may occur in the absence of significant epicardial CAD Myocardial O 2 supply/demand mismatch o high afterload o myocardial perfusion gradient o myocardial mass o coronary flow reserve (CFR)

11 Survival (%) Symptomatic AS: the Effect of AVR AVR improves: Survival EF NYHA class LV mass Years Schwartz F, et al. Circ 2002

12 AS: Important facts (cont d) Any calcific AoV disease is associated with increased mortality If untreated, symptomatic severe diseases is universally fatal! ~ 50% of pts with severe AS also have severe CAD (preop cath) Rosenhek L, et al NEJM 2000

13 Conceptual Framework Natural History of Calcific AoV Disease AVR at symptom onset CAD? Otto CM, EHJ 2009

14 Aortic Stenosis and CAD Important facts Links AS/CAD o risk factors o pathogenesis o statins Management

15 Calcific (degenerative) AS Associated with: Increasing age Male gender Hypertension Hypercholesterolemia Smoking Renal dysfunction

16 Factors Associated with AoV Degeneration 953 subjects, yrs, random sample Germans, echo F/U 10 years Prevalence odds ratio Stritzke J, et al. KORA/MONICA Survey, EHJ 2009

17 Early Lesion of Degenerative Valvular AS Hypotheses: Ca ++ Mechanical stress wear and tear Active process inflammation? Otto C, et al. Circ 1994

18 Histological Studies of Aortic Valve Leaflets Otto C, et al. Circ 1994

19 Immunhistochemistry studies of Aortic Valve Leaflets Otto C, et al. Circ 1994

20 Histological Studies of Aortic Valve Leaflets Otto C, et al. Circ 1994

21 Free of CVS event CVS Event-Free Survival in Pts with AoV Sclerosis vs. Normal AoV 960 (11%) pts included in LIFE-echo substudy Composite CVS endpoint: CVS death, MI and Stroke F/U > 4 yrs Normal AoV HR: 1 AoV Sclerosis HR: 2.0 P<0.01 Time (months) Olsen MH, et al AJC 2005

22 Free of CVS event CVS Event-Free Survival in Pts with AoV Sclerosis vs. Normal AoV with/without CAD 960 (11%) pts included in LIFE-echo substudy Composite CVS endpoint: CVS death, MI and Stroke F/U > 4 yrs Normal AoV, no CAD HR: 1 AoV Sclerosis, no CAD HR: 2.0, P<0.01 Normal AoV+CAD HR: 2.6, P=0.001 AoV Sclerosis+CAD HR: 4.4, P<0.001 Time (months) Olsen MH, et al AJC 2005

23 Why is Ao Sclerosis associated with Adverse Outcomes? Proposed mechanisms: Marker of diffuse atherosclerosis Endothelial dysfunction Altered calcium metabolism Lipid accumulation Genetic polymorphisms Common patophysiology: inflammation Otto K. JACC 2004

24 Event-free* Survival in pts Presented with Chest Pain in the ER according to the Severity of AoV sclerosis *, cardiac death and non-fatal MI Chandra HR, et al. JACC 2004

25 Cardiac death and nonfatal MI at index admission or at 1-year F/U in pts with ER chest pain in relation to AoV sclerosis, CAD and systemic inflammation Chandra HR, et al. JACC 2004

26 Factors Associated with Cardiac Death and Nonfatal MI at Admission or at 1-year in Pts with ER chest pain HR P value Chandra HR, et al. JACC 2004

27 Calcific Aortic Valve Disease Challenge to identify: Factors that predict transition from patient at risk to a patient with aortic sclerosis Which aortic sclerosis patient will go on to progressive aortic stenosis

28 Plasma Campesterol : Lathosterol Plasma Campesterol-to-Lathosterol Ratio Increases with CAD Severity in pts with AS Campesterol CHL absorption Lathosterol CHL synthesis *, p< VD vs. 0-VD * Coronary artery disease (extent) Weingartner O, at al. Coron Art Dis 2009

29 Plasma and Aortic Valve Cusps Campesterol-to-Lathosterol Ratio and Family History of CVD p<0.005 p<0.05 Weingartner O, at al. Coron Art Dis 2009

30 Prediction of Concomitant CAD in Pts with AS Weingartner O, at al. Coron Art Dis 2009

31 Cholesterol, CAD and AS Alterations in cholesterol homeostasis are associated with CAD in pts with AS Enhanced absorption and reduced synthesis of cholesterol is related to a positive family history of CVD and the development of concomitant CAD in pts with AS. Weingartner O, at al. Coron Art Dis 2009

32 Coronary Flow Reserve Coronary Flow Reserve is Impaired in Pts With AoV Calcifications before AS Develops p<0.001 Endothelial dysfunction is present in early stages of calcific AoV disease Control AoV Calc Bozbas H, et al. Atherosclerosis 2007

33 Increased Temperature Variability within the Leaflets and Evidence of Inflammation AS AoV Stenosis AoV Insufficiency Intensive inflammatatory cell infiltration Normal valvular stroma with sparse cellularity Anti TNFα + Anti TNFα - Termal ( C) heterogeneity 1.52 ± ± 0.11 p=0.01 Toutouzas K, et al. JACC 2008

34 Temperature differences (DT) in AoV Leaflets With Intense vs. Low Expression of Inflammatory Indexes Toutouzas K, et al. JACC 2008

35 Statins and Progression of AS Rate of Annual Increase of Vmax 1046 pts with Ao sclerosis, mild and moderate AS 309 pts on statins 2 ECHOs (>2 yrs apart), F/U 5.6 yrs Ao sclerosis P = 0.01 Independent Moderate Mild AS AS predictors of P p = progression: Statins Initial Vmax Dialysis No Statins Statins No Statins Statins Antonini-Canterin F, et al AJC 2008

36 From Evolution of Understanding of Aortic Stenosis Degenerative disease We do not what is going on here (B. Carabelo) To Active inflammatory process, with much in common with CAD

37 Aortic Stenosis and CAD Important facts Links AS/CAD o risk factors o pathogenesis o statins Management

38 Calcific Aortic Valve Disease: Patient Management o Aortic sclerosis Risk factor evaluation and reduction F/U o Aortic stenosis Severity Symptoms LV response Other valves High risk features Timing of Surgery

39 High-Risk Features in AS Very severe AS Rapidly increasing severity of AS LV ischaemia Coronary artery disease LV systolic dysfunction Clinical afterload mismatch Marked or excessive LV mass LV diastolic dysfunction Older age Positive exercise test Non-cardiac co-morbide conditions

40 ESC Guidelines 2007

41 Operative Mortality After AVR STS, Society of Thoracic Surgeons (USA) (incl REDO) UKCSR, UK Cardiac Surgical Register EHS, Euro Heart Survey ESC VHD Guidelines 2007

42 Clinical Challenge How to manage pts with mild-to-moderate AS who need CABG? AS could be detected: o PreOp (expected) o IntraOp (unexpected)

43 CABG and moderate AS Issues to be considered Progression rate of AS Lifespan

44 Individual Variability in the Rate of Hemodynamic Progression of Asymptomatic AS Otto, C. M. et al. Circulation 1997;95:

45 Severity of AoV Calcifications Predict Survival in Asymptomatic Severe AS 126 pts, asymptomatic severe AS F/U for death+avr (symptoms) Calcifications Event free Survival 1 y 2 yrs 4 yrs No or Mild 92+5% 84+8% 75+9% Moderate or Severe 60+6%* 47+6%* 20+5%* *, P<0.001 Rosenhek R et al., NEJM 2000

46 CABG and moderate AS Issues to be considered Progression rate of AS Lifespan CABG only: o expose pt to higher risk of REDO for AVR Concomitant CABG+AVR: o avoids the risk of REDO for AVR o higher periop risk o prosthesis related complications

47 Operative Mortality for AVR in Octogenarians Very low, if: EF > 50% Not REDO or Emerg Langanay T, et al. J Heart Valve Dis 2006

48 PeriOp Results in Elderly Pts (>70 yrs) and Moderate AS undergoing CABG/CABG+AVR Degenais F, et al Ann Thorac Surg 2010

49 Survival Survival in Pts with significant Comorbidities Degenais F, et al Ann Thorac Surg 2010

50 Long-term Outcome in Pts >70yrs with Moderate AS undergoing CABG/CABG+AVR Survival Freedom for AVR 65% at 5 yrs 98% at 5 yrs ROC: AoV gradient 26/15mmHg Degenais F, et al Ann Thorac Surg 2010

51 Strategy for AVR in Pts Undergoing CABG CABG/AVR preferred 28 mmhg CABG preferred Smith WT, et al. JACC 2004

52 Survival Survival of Pts with AS undergoing CABG alone vs. AVR+CABG Moderate AS AVA cm 2 Mild AS AVA > 1.5 cm 2 CABG+AVR CABG+AVR p= CABG p=0.46 CABG Progression of 6.5 mmhg/year (gradient), or >0.45 m/s/year (jet velocity) indicate worse survival/need avr Years Quere JP, et al. Circ 2006

53 Management of Previously Undetected AS During CABG Moderate/severe AS: AVR indicated at the time of primary procedure (lower mortality of combined vs. REDO surgery) Mild AS: AVR controversial, but may be considered if valve is moderately to severe calcified (rapid progression likely) 2008 Focused Update Incorporated Into the ACC/AHA 2006 Guidelines for the Management of Patients With Valvular Heart Disease

54 IntraOp Quantification of AS Adequate and careful preop workup is mandatory IntraOp quantification of AS in the anesthetized patient is always tricky The need for it should be kept to a minimum!

55 AVR in pts undergoing CABG Summary Definitely yes, if severe AS Probably yes, if moderate AS especially if rapidly progressive Probably not, if mild AS except mild AS with severe calcif (rare) Dependent on age

56 Take Home Message AS and CAD Similar risk factors Similar pathogenesis (?) If combined, CV risk is higher Careful consideration for concomitant AVR+CABG