Asymptomatic Severe Valve Disease Risk Stratification Raphael Rosenhek Department of Cardiology Medical University of Vienna Journées Européennes de la SFC Paris, January 18 th 2019
Disclosure Statement of Financial Interest I currently have, or have had over the last two years, an affiliation or financial interests or interests of any order with a company or I receive compensation or fees or research grants with a commercial company : Speaker's name : Rosenhek, Raphael, Vienna ☑ Je n'ai pas de lien d'intérêt potentiel à déclarer
Timing of Intervention in Mitral Regurgitation Impact of Preoperative Symptoms on Survival NYHA I-II NYHA III-IV Years Tribouilloy C et al. Circulation 1999;99:400
Severe Aortic Stenosis Prognosis of Symptomatic Patients Onset of severe 100 symptoms Latent period failure (increasing obstruction, 80 syncope Myocardial overload) angina Survival (%) 60 2 3 5 Average survival (yrs) 40 20 Average age of death 0 40 50 60 63 70 80 Age (yrs) Ross, Braunwald. Circulation 1968
Severe „asymptomatic “ Aortic Stenosis Exercise-testing 1,0 Negative (22 patients) 0,8 Event-free Survival Positive test: symptoms (n=23) 0,6 BP increase < 20mmHg ST segment depression > 2mm 0,4 Complex vent. arrhyth. 0,2 Positive (44 patients) P=0.0001 n=66 0 0 12 24 36 48 60 Time (months) Amato, MC. Heart 2001;86:381-386
Severe Aortic Stenosis Role of Exercise-testing Predictive value: onset of spontaneous symptoms within 12 mths n = 125 Predictor NPV PPV Absence of symptoms 87% 57% physically active, <70yrs 79% Abnormal BP response 78% 48% ST depression > 2mm 77% 45% Das, P. Eur Heart J 2005;26:1309-1313
Severe but Asymptomatic MR Early Surgery vs „Waiting for Symptoms“ Registry No surgical mortality neither in the OP nor in the CONV group ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? 17 pts lost to follow-up + + + apparently all in the OP group 3 unaccounted “ Noncardiac deaths” in the surgical group 2 strokes, 1 infection No conclusive answer Events in the “conventional” group: 22 heart failure (trigger for surgery) 5 congestive heart failure deaths in pts refusing surgery 1 sudden death in a patient who became symptomatic Kang, D.-H. et al. Circulation 2009;119:797-804
Severe but Asymptomatic MR Early Surgery vs „Waiting for Symptoms“ Registry Lower rate of cardiac mortality and of cardiac events only in pts ≥ 50 yrs Kang DH et al. J Am Coll Cardiol 2014;63:2398-2407
MIDA: Outcome in Severe Flail MR Early Surgery vs „ Watchful Waiting“ Retrospective registry 6 centers – 24 years (1980-2004) 1021 of 2097 pts without a class I 19% with class II indication (AFib 10%, PHT 11.8%) indication for surgery Propensity score matched cohort Arbitrary Cutoff: Early surgery defined as “within 3 months of diagnosis” Watchful Waiting?: „ Each patient had follow-up visits with a physician within each participating center or elsewhere “ Suri RM. et al. JAMA 2013;310:609-16
Early Surgery vs. “Conventional Treatment” Very Severe Aortic Stenosis Surgery n = 197 AV- Vel ≥ 4.5 m/s mGrad ≥ 50 mmHg AVA ≤ 0.75 cm 2 Conventional „In a separate analysis in which patients of the conventional treatment group were censored at symptom onset, cardiac mortality rates were 5 ± 2%, 9 ± 3% and 14 ± 6% at 2,4 and 6 yrs P < 0.001 ( P=0.0018) “ Years Kang, D. H. et al. Circulation 2010;121:1502-1509
Early Surgery vs. “Conventional Treatment” Aortic Stenosis Taniguchi et al. The Annals of Thoracic Surgery 2006 82, 2116-2122
Early Surgery vs. “Conventional Treatment” Very Severe Aortic Stenosis Metanalysis: All-cause Mortality Généreux P et al. J Am Coll Cardiol 2016;67:2263-2288
Asymptomatic Severe Aortic Stenosis Overall Outcome: Wait for Symptoms Strategy General Population 126 Patients 100 Severe AS (AV-Vel ≥ 4m/s) 90 Asymptomatic 80 Patients with Aortic Stenosis Survival (%) 70 Compared to Age-, Gender- Matched General Population 60 50 40 30 Regular Control exams 20 10 P = n.s. 0 0 1 2 3 4 5 Rosenhek, R. et al. Years N Engl J Med 2000;343:611-617
Asymptomatic Severe Mitral Regurgitation Survival - Watchful Waiting Strategy 1 0 0 1 0 0 9 0 9 0 92% 8 0 8 0 78% 7 0 7 0 65% 6 0 55% 6 0 5 0 5 0 4 0 4 0 All patients 3 0 3 0 Patients with flail leaflet 2 0 2 0 Expected survival 1 0 1 0 P = n.s. 0 0 0 1 2 3 4 5 6 7 8 0 1 2 3 4 5 6 7 8 Years Years Rosenhek et al. Circulation 2006;113:2238-2244.
Asymptomatic Severe Mitral Regurgitation 15 Yr Outcome – Active Surveillance Survival Event-Free Survival Zilberszac R ... Rosenhek R. JACC CVI 2018;11:1213-1221
EORP VHD II 2017 Characteristics of Operated Patients AS AR MS MR 866 93 109 367 n= Age (years) 75 57 56 66 [66-83] [48-69] [44-63] [57-74] Female (%) 44 17 77 42 NYHA III-IV (%) 48 34 52 43 LVEF ≥60% (%) 54 30 53 43 Charlson index 4 [3-6] 2 [1-3] 2 [1-3] 3 [2-5] Euroscore II 2.0 1.1 1.1 1.9 [1.2-3.5] [0.8-1.9] [0.8-2.5] [1.0-3.7] Iung B et al. ESC 2018.
Waiting Times for Aortic Stenosis Surgery Assessing Practice All residents of British Columbia on a Waiting List Between 1991 and 2000 Munt B. et al. Can J Cardiol 2006;22:497-502
Valvular Heart Disease Elective Surgery? Risk Stratification Risk Benefit • Risk of Surgery • Late Symptom Reporting • Prosth. Complications • Risk of death on waiting list - Thromboembolism • Higher operative mortality for more - Bleeding symptomatic pts. - Endocarditis • Risk of sudden death - Paravalvular Regurgitation • Myocardial damage - Valve Thrombosis • Need for reoperation Modified from Rosenhek, R. et al. Eur Heart J 2002;23:1417-21
Mitral Regurgitation Quantification MR Quantification by Echo and MRI Regurgitant Volume Regurgitant Fraction Lopez-Mattei J. et al. Am J Cardiol 2016;117:264-270
Survival in Mitral Regurgitation Severity of MR Antoine C et al. Circulation 2018;138:1317-1326
Natural History Velocity vs. Valve Area AVA < 1 cm 2 Sensitive AV-Vel ≥ 4.0 m/s Minners, J. et al. Specific Eur Heart J 2008 29:1043-1048
Aortic Stenosis Quantification Dimensionless Index TVI LVOT /TVI AV 488 patients with preserved (≥50%) ejection fraction and no or minimal subjective symptoms, diagnosed with ≥ mild AS Rusinaru D et al JACC Cardiovascular Imaging, Volume 8, Issue 7, 2015, 766 – 775
Severity of Aortic Stenosis Natural History AV-Vel 2.5 to 3.0 m/s Event-free Survival (%) AV-Vel 3.0 to 4.0 m/s AV-Vel 4.0 to 5.0 m/s 64 mmHg 100 mmHg AV-Vel 5.0 to 5.5 m/s 121 mmHg AV- Vel ≥ 5.5 m/s P < 0.0001 Years Rosenhek R et al. Eur Heart J 2004;25:199-205 Rosenhek R et al. N Engl J Med 2000;343:611-617 Rosenhek R et al. Circulation 2010;121:151-156
Life Expectancy in Years Europe and US EU US Age Overall Men Women Overall Men Women 65 18.9 17.0 20.5 18.5 17.0 19.7 70 15.2 13.5 16.5 14.9 13.6 15.9 75 11.8 10.5 12.7 11.6 10.5 12.3 80 8.8 7.9 9.4 8.7 7.8 9.3 85 6.5 5.9 6.8 6.4 5.7 6.8 90 4.6 4.1 4.8 95 3.2 2.9 3.3 100 2.3 2.0 2.3 ESC Working Group on Valvular Heart Disease Position Paper. Assessing the Risk of Interventions in Patients with Valvular Heart Disease Rosenhek R et al. Eur Heart J 2012;33:822-828
Severe Asympt AS in the Elderly ≥ 70 yrs Event-free Survival 100 100 30% impaired Mobility 90 9 cardiac deaths Event-free Survival (%) 90 80 80 70 70 60 60 AV-Vel 4-5 m/s Age 70-80 years 50 50 40 40 30 30 AV-Vel ≥ 5 m/s 20 20 Age ≥ 80 years 10 10 P = 0.84 P = 0.84 P < 0.001 P = 0.84 0 0 0 1 2 3 4 0 1 2 3 4 Years Years Zilberszac R et al. J Am Coll Cardiol Cardiovasc Imaging 2017;10:43-50
Aortic Stenosis Ventricular Response Lindman B et al. Nat Rev Dis Primers. 2016;2:1-28.
Severe Aortic Stenosis Valve Calcification and Rapid Progression Patients with moderate or 100 severe aortic valve Event-free Survival (%) 90 calcification 80 and 70 aortic jet velocity increase 60 > 0.3 m/s within 12 months 50 40 30 2 year event-rate: 80% 20 10 0 0 1 2 3 4 5 Time from observation Rosenhek, R. et al. of rapid progression (days) N Engl J Med 2000;343:611-617
Aortic Stenosis Survival: BNPratio Clavel MA et al. J Am Col Cardiol 2014;63:2016-25
Aortic Stenosis - MRI Midwall Fibrosis Survival Midwall Fibrosis Is an Independent Predictor of Mortality in Patients With Aortic Stenosis Dweck MR et al. JACC, Volume 58, Issue 12, 2011, 1271 – 1279
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