Severe aortic stenosis should be operated before symptom onset CONTRA Helmut Baumgartner Westfälische Wilhelms-Universität Münster Adult Congenital and Valvular Heart Disease Center Dept. of Cardiology and Angiology University Hospital Muenster
DECLARATION OF CONFLICT OF INTEREST No disclosures
Aortic Valve Replacement for Asymptomatic Aortic Stenosis? Risk Operative risk (1-) 3-4%; elderly 4-8%) Prosthetic valve related complications Thromboembolism Bleeding Endocarditis Parivalv. leak Valve thrombosis Re-intervention Autograft (Ross Op.) Homograft Bioprostheseis 1-2%/yr 1-2%/yr 0.3%/yr 0.3%/yr Benefit Avoid Sudden Death Avoid irreversible myocardial damage (LVH / fibrosis) Reduce operative risk Improve postop. Outcome (survival, morbidity)
SURVIVAL (%) Natural History of Asymptomatic, Hemodynamically Significant AS N = 113 (prospective) 80-60 - 40-20 - Patients (censored at symptoms or intervention) Age- and gender matched control subjects 0-0 1 2 3 4 Years Pellikka PA et al, JACC 1990
Sudden Death in Asymptomatic AS Study (year) Kelly et al (1988) Pellikka et al (1990) Otto et al (1997) Rosenhek et al (2000) Pellikka et al (2005) Rosenhek et al (2010) Kang et al (2010) Number of Patients Mean FU (months) Severity of AS Sudden Deaths 51 18 PV > 3.5 0 113 20 PV > 4.0 (2) 0 w/o prec. sympt 114 30 PV 3.6±0.6 104 27 PV > 4.0 1 622 65 PV > 4.0 11 (6?) (5 w/o FU 1yr!) 116 41 (median) 0 PV > 5.0 1 95 58 PV > 4.5 9 PV = peak velocity
Aortic Stenosis - Risk Stratification Role of Exercise Testing 4 sudden deaths! (3 with symptoms on ex.) MCM Amato et al Heart 2001;86:381
Aortic Stenosis - Risk Stratification by Exercise Testing Das P et al Eur Heart J 2005 N=125 FU 12 months No sudden death! Predictor NPV PPV Absence of symptoms* 87% 57% physically active, <70yrs 79% Abnormal BP response 78% 48% ST depression > 2mm 77% 45% * 83% of pts. with dizziness, 50% with SOB and 57% with AP developed symptoms
Severe asymptomatic AS: Predictive value of neurohormones Symptom-Free Survival of Pts. with Severe AS (%) (Kaplan Meier Analysis) 100 100 80 80 60 p< 0.01 60 p< 0.001 40 40 20 BNP < 130 BNP 130 20 Nt BNP < 80 Nt BNP 80 0 0 0 100 200 300 400 0 100 200 300 400 Follow-up Days Follow-up Days Bergler-Klein J...Baumgartner H: Circulation 2004;109:2302-8
Aortic Jet Velocity and Outcome of AS Otto CM, et al. Circulation 1997;95:2262-2270
Event-Free Survival: Extent of AV calcification no or mild calcification p < 0.0001 Events: Development of symtoms Death Moderate or severe calcification Event-days Rosenhek et al N Engl J Med 2000
Combined information: Aortic valve calcification and rate of progression Event-free Survival Patients with moderate or severe aortic valve calcification and aortic jet velocity increase 0.3 m/s within 12 months 2 year event-rate: 80% Time from observation of rapid progression (days) Rosenhek et al N Engl J Med 2000
Severe asymptomatic AS: Predictive value of neurohormones B-type natriuretic peptide and long-axis left ventricular dysfuncion Lancellotti P et al: Am J Cardiol 2010;105:383-8
Risk Score for Predicting Outcome in Patients With Asymptomatic AS 107 pts. with asymptomatic AS (3.5 4.4m/s), mean age 72 yrs Endpoint: AVR for symptoms or positive ET, death Independent Predictors of Outcome: Female sex Peak velocity BNP Score validated in an independent cohort of 107 pts) Score: [Vpeak x 2] + (logbnp x 1.5) + 1.5 (if female sex) JL Monin et al Circulation 2009;120:65-79
Exercise Echocardiography in Asymptomatic AS 135 asympt. pts. with at least moderate AS and normal standard exercise test Maréchaux S et al: Eur Heart J 2010;31:1295-7
Prognostic value of inappropriately high LV mass in asympt. severe AS 209 asympt. pts. with severe AS Endpoint: death from all causes, AVR, admission for MI or CHF Cioffi et al: Heart 2010;[Epub ahead of print]
Predictors of Outcome in Asymptomatic AS Clinical: older age, presence of CV risk factors Echocardiography: higher peak velocity, severe calcification, rapid hemodynamic progression, reduced LVEF, excessive LVH, increase in gradient with exercise Exercise testing: symptoms on exercise (blood pressure fall) Biomarkers: markedly elevated natriuretic peptides (BNP, Nt-proBNP)
Aortic Jet Velocity - Outcome of AS 116 pts. AV Vel >5m/s Median FU 41 mo 96 events: AVR (90) Sudden death (1) Deaths possibly cardiac related (5): mean age 83yrs MCI (1) Sepsis / multiorgan failure (3) CHF (1) Rosenhek R et al. Circulation 2010;121:151-156
SURVIVAL(%) Asymptomatic Aortic Stenosis Wait for Symptoms Strategy 100 90 80 70 60 50 40 30 20 10 General Population Patients with Aortic Stenosis Overall survival among 126 patients with asymptomatic but severe aortic stenosis, as compared with ageand sex-matched persons in the general population 0 0 1 2 3 4 5 Years Rosenhek, R Baumgartner H N Engl J Med 2000;343:611-617
Early surgery vs. conventional treatment in asymptomatic severe AS Age 63±12 yrs Peak V 4.5m/s Age, gender, EuroSCORE, EF similar Median FU 4.1 yrs Kang DH et al Circulation 2010;121:1502-9
Early surgery vs. conventional treatment in asymptomatic severe AS Kang DH et al Circulation 2010;121:1502-9
Early surgery vs. conventional treatment in asymptomatic severe AS Kang DH et al Circulation 2010;121:1502-9
Limitations of Kang s study Groups cannot be comparable - noncardiac deaths 2.9 vs 10.5% in surgical vs. conservative group - operative mortality 0%, cardiac mortality 0% - coronary artery disease in only 6% 22% of pts. who developed symptoms not treated! (10 of 18 cardiac deaths occurred in this group!) Markedly higher sudden death rate than observed in any previous study (7 of 36 asympt. pts.!!!) No exercise test (pts. inappropriately assigned to the asymptomatic group?)
Benefits of Early Valve Replacement in Asymptomatic AS 100 80 N = 622 age 72±11 years isolated severe asympt. AS SURVIVAL (%) 60 40 20 0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 Years AVR, no symptoms AVR, symptoms No AVR, no symptoms No AVR, symptoms Retrospective, last med. contact to death: 1.7±2.1 yrs Brown ML et al. J Thorac Cardiovasc Surg 2008;135:308
SURVIVAL (%) Benefits of Early Valve Replacement in Asymptomatic AS 100 80 60 Asymptomatic at operation Symptomatic at operation P = 0.919 40 20 Operative mortality: 2 vs 1% (n.s.) 0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 Years Brown ML et al. J Thorac Cardiovasc Surg 2008;135:308
Clnical Outcome of Asympt. AS With Medical and Surgical Management: Importance of STS Score at Diagnosis N = 694 Age 71 ± 11 yrs Peak Vel > 4.0 m/s Pts. who had surgery within 1 year were: Older More comorbidities Higher STS score Higher EuroSCORE Le Tourneau Th et al Ann Thorac Surg 2010;90:1876
Percent cumulative survival To operate or not on elderly patients with AS: the decision and its consequences 100 Bouma BJ et al Heart 1999;82:143-8 RISK SCORE (impaired LV-function, moderate or more MR, angina and/or dyspnea class III or IV): LOW INTERMEDIATE HIGH 80 60 40 20 0 Med. treated Surg. treated Med. treated Surg. treated Med. treated Surg. treated 0 12 24 36 Time (months) 0 12 24 36 Time (months) 0 12 24 36 Time (months)
Surgery in asymptomatic AS? The very rare asympt. patient with reduced EF (without other explanation) should have surgery Asymptomatic status must be carefully confirmed including exercise testing in physically active pts. Other risk factors primarily predict the development of symptoms and requirement of surgery (not a worse survival with watchful waiting) However, there is no evidence what so ever that truly asymptomatic patients with normal EF benefit from early surgery!