Natural History and Echo Evaluation of Aortic Stenosis Prof. Patrizio LANCELLOTTI, MD, PhD Heart Valve Clinic, University of Liège, CHU Sart Tilman, Liège, BELGIUM
AORTIC STENOSIS First valvular disease in Europe 3-6% of subjects > 65 years First operated valvular disease in developed countries Degenerative: 50 % Rheumatic 10 % Bicuspid: 40 % Roberts & Ko. Circulation. 2005; 111: 920-5
NATURAL HISTORY OF AS 100 80 60 40 20 0 Asymptomatic period (increasing obstruction, myocardial overload) Onset of severe symptoms Angina Syncope Failure 0 2 4 6 Average survival (yrs) Average death age (male) 0 40 50 60 70 80 Age (years) Ross, Braunwald 1968
Cumulative survival (%) Severe Symptomatic Aortic Stenosis 100 Surgery vs. Conservative 80 60 Patients having undergone AVR because of severe AS (n=314) 40 20 0 P<0.0001 Patients with severe AS who refused surgery (n=35) 2 4 6 8 10 Time (yrs) Horstkotte Eur Heart J 1988;9:57-64
INDICATIONS FOR AVR IN AS SEVERE STENOSIS Peak velocity: 4 m/s Mean gradient: 40 mmhg Aortic valve area (AVA): 1.0 cm 2 Indexed AVA: 0.6 cm 2 /m 2 + SYMPTOMS and/or LVEF<50% = AVR (Class I, B)
AORTIC VALVE AREA
EVALUATION OF AORTIC STENOSIS 3D-Echo Assessment (41 pts) Gutierrez-Chico J et al. Eur Heart J 2007
HYPERTENSION TENDS TO MASK AS SEVERITY Changes in AVA are parallel to changes in Q mean and not changes in SVR/SAC Severe AS + no HPT Severe AS + HPT Kadem, L et al. Heart 2005;91:354-361 Little, S. H et al. Heart 2007;93:848-855
Preserved LV Ejection Fraction Normal Flow, High Gradient SVi > 35 ml/m² Gr > 40 mmhg AVA 0.4 0.1 cm/m² EDD 48±5 mm N=152 (30%) AVR = 80% Low Flow, High Gradient SVi 35 ml/m² Gr > 40 mmhg AVA 0.3 0.1 cm/m² EDD 43±5 mm N=44 (8%) AVR = 68% Normal Flow, Low Gradient SVi > 35 ml/m² Gr 40 mmhg AVA 0.5 0.1 cm/m² EDD 48±5 mm N=193 (38%) AVR = 53% Low Flow, Low Gradient SVi 35 ml/m² Gr 40 mmhg AVA 0.5 0.1 cm/m² EDD 46±5 mm N=123 (24%) AVR = 36% Dumesnil et al, Eur H J 2009
Low Flow, Low Gradient Normal Low Flow Paradoxical Low Flow LV EF markedly underestimates the extent of myocardial systolic impairment Lancellotti et al. Eur J Echo 2010 Weideman et al. Circulation 2009
Should Early Elective Surgery be performed in Severe Asymptomatic AS? Good Prognosis Sudden death: 0.3% to 1% per year - Risk of rapid progression - Risk of irreversible myocardial damage Operative risk: < 2% Valve prosthesis complications: - operative mortality in severely symptomatic pts 1 to 3% per year - Mortality on the waiting list up to 15%? - Risk related to delayed symptom reporting - Event at 2 years : varying : 21 to 67 % Medical Management or Aortic Valve Replacement
Risk Stratification in Asymptomatic AS Higher Risk Age, renal failure, inactivity, CAD V max > 4.5 m/s Rapid Ao Vmax increase > 0.3 m/s/y + Mod/Severe Ca 2+ Abnormal exercise testing Otto Circ 1997, Rosenhek NEJM 2000, Pellika Circ 2005, Amato Heart 2001
Indications for AVR in AV Stenosis ACC/AHA/ESC Practice Guidelines Asymptomatic pts with severe AS ESC 2007 if LV EF < 50% if symptoms if fall in SBP Arrhythmias IC I C IIa C IIb C
Das, P. Eur Heart J 2005;26:1309-1313 Role of Exercise-testing in AS Predictive value for onset of spontaneous symptoms within 12 months n = 125 Predictor NPV PPV Symptoms during exercise (p<0.001)(dizziness) whole population 87% 57% physically active, <70yrs 79% limited activity 41% Abnormal BP response (p=ns) 78% 48% ST depression > 2mm (p=ns) 77% 45%
Effects of AS on Myocardial Function and Structure LV Concentric Remodeling Diastolic dysfunction LA pressure LA dilatation Systolic dysfunction: Subendocard. fibrosis Consider valve, ventricle, ventricular-vascular coupling (BNP release)
Left Ventricular Afterload in Aortic Stenosis = Valvular Load + Arterial Load SV EOA AA Static Pressure LVSP P MG SAP } } Arterial Valvular Load Load }Total Load Flow axis Valvulo-Arterial Impedance LVSP Z va = = MG + SAP SVi SVi Hachicha et al., Circulation, 2007
Overall Survival, (%) Prognostic Impact of Global Afterload Retrospective analysis of 544 asymptomatic pts moderate AS ( 2.5 m/s), LVEF 50%; Follow-up 2.5 1.8 years 100 80 60 40 20 0 P < 0.001 Age-Gender matched general population 0 2 4 6 8 Follow-up (years) Z va <3.5 3.5 Z va <4.5 Z va 4.5 3 years 88 3% 80 3% 70 5% Multivariate Analysis 3.5 Z va <4.5: 2.3; p=0.03 Z va 4.5: 2.8; p=0.01 Hachicha et al., JACC, 2009
Brain Natriuretic Peptide in Asymptomatic AS Severity of AS LV mass Symptomatic status NYHA Class Systolic dysfunction Symptom free survival n=43 pts Bergler-klein Circulation 2004, Nessmith AJC 2005, Weber EHJ 2004, Lim, EHJ 2004, Kupari Eur JHF 2007
Risk Score for predicting outcome in asymptomatic AS 107 pts followed in Créteil Risk score according to independent variables Validation in Liège (107 pts) Score = (Peak velocity x 2) + (nat log BNP x 1.5) +1.5 (if female) Obs erved 24-month event rates (% ) 100 90 80 70 60 50 40 30 20 10 0 < 10% 7 9 11 13 15 17 19 21 23 16 > 75% R is k S c ore value Monin, Lancellotti et al. Circulation, 2009
Multivariate Analysis Adjustment for gender, systemic arterial compliance, E-wave, E/A ratio and response to exercise (abnormal vs. normal) Peak aortic velocity 4.4 m.s -1 Zva 4.9 mmhg.ml -1.m -2 Longitudinal strain 15.9 % Ind. LA area 12.2 cm 2 /m 2 HR= 1.7, p=0.027 HR= 1.9, p=0.013 HR= 2.2, p=0.003 HR= 2.8, p=0.001 0 1 2 3 4 5 Hazard-ratio Lancellotti et al. Am J Cardiol 2010 Lancellotti et al. Heart 2010 6
Event-free Survival, % 100 Impact of Cumulative Number of Predictive Variable p<0.001 80 60 76 6% 73 10% 73 10% 70 8% Risk Factor =0, (n=20) Risk Factor =1, (n=56) 40 20 0 40 8% 35 8% 15 8% 10 6% 0 1 2 3 4 5 6 Follow-up, years Risk Factors =2, (n=57) Risk Factors 3, (n=30) 7
Prognostic imapct of exercise Echo in AS Incremental prognostic value of Exercise Doppler Echo Lancellotti et al Circulation 2005;112:I-377 I-382 Maréchaux et al Echocardiography 2007
Prognostic impact of exercise echo in AS Patients with normal exercise test Maréchaux et al, Eur H J 2010; April 10
Conclusions In symptomatic patients with severe AS surgery is warranted The prognosis of asymptomatic is highly variable Risk stratification is mandatory A normal exercise test predicts good 1-year outcome (<70-y and physically active pts) Clinical outcome can be predicted by measurements that integrate the «3-V» components Exercise echo provides incremental prognostic value in pts with normal exercise test