Exercise Testing/Echocardiography in Asymptomatic AS

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Exercise Testing/Echocardiography in Asymptomatic AS Raluca Dulgheru, MD Heart Valve Clinic, University of Liège, CHU Sart Tilman, BELGIUM

Disclosure related to this presentation: None

VALVULAR HEART DISEASE Prevalence First valvular disease in Europe Severe AS Pooled prevalence in the elderly (>75 y) 3.4% (4.9 million pts in EU) 50% are asymptomatic

Management in severe AS - Surgery when symptoms develop - Asymptomatic patients matter of debate risk of sudden death risk of surgery risk of rapid progression risks related to the presence of a risk of irreversible myocardial prosthesis: damage hemorrhagic risk of shifting into a higher thrombotic surgical risk category prothesis dysfunction endocarditis Otto Circulation 1997, Rosenheck NEJM 2000, Pellika Circulation 2005

Management in asymptomatic severe AS - based on a risk stratification algorithm rest echocardiographic parameters (LVEF<50%, Vmax, Vmax progression, calcification +++, LVH, PHT, GLS, Zva, LA area etc ) exercise stress testing (exercise echocardiography) natriuretic peptides BNP/Nt-pro-BNP (rest and exercise) MDCT (Aortic Valve Calcium scoring) CMR (Mid-wall fibrosis) PET/CT (?) Otto Circulation 1997, Rosenheck NEJM 2000, Pellika Circulation 2005

Role of exercise testing/echocardiography for risk stratification in asymptomatic severe AS? Otto Circulation 1997, Rosenheck NEJM 2000, Pellika Circulation 2005

Prevalence of normal stress test Limiting symptoms in more than 1/3 Rafique et al. AJC, 2009

For unmasking symptoms in patients who claim to be asymptomatic

Risk Stratification with Exercise Testing 30 asymptomatic patients, age = 62±14 years, AVA = 0.7±0.2 cm², Peak Gradient = 79±21 mm Hg Negative test Positive test p<0.0002 0 70 140 months Alborino D et al J Heart Valve D 2002; 11:204 Courtesy of dr. J Magne

Prognostic Value of Exercise Test in AS Meta-analysis: 7 studies, 2002-2007 491 pts Risk for CV cardiac events events Sudden-death Risk n=9, of sudden 100% abnormal death (n=362) test OR: 0.12 (0.07-0.21) p<0.000001 OR: 0.18 (0.03-1.01) p=0.05 Rafique et al. AJC, 2009 5% of pts with abnormal stress test vs. 0%

For Individual Risk Stratification To aid to Clinical Decision Making and Guide the Type of Treatment

Indications for AVR in AV Stenosis ACC/AHA/ESC Practice Guidelines Asymptomatic pts with severe AS ACC/AHA (2008) Symptoms or Fall in SBP IIb C ESC (2012) if symptoms if fall in SBP I C IIa C

Indications for AVR in AV Stenosis ACC/AHA/ESC Practice Guidelines Asymptomatic pts with severe AS ACC/AHA (2014) Symptoms during exercise testing (I) Decreased exercise tolerance or Fall in SBP (IIa) ESC (2012) if symptoms if fall in SBP I IIa Physically active, <70yrs

Role of Exercise-testing in AS Predictive value for onset of spontaneous symptoms within 12 months (125 pts) Predictor NPV PPV Symptoms during exercise (p<0.001) (dizziness) whole population 87% 57% physically active, <70yrs 79% limited activity (> 70 yrs) 41% Abnormal BP response (p=ns) 78% 48% ST depression > 2mm (p=ns) 77% 45% Das, P. Eur Heart J 2005;26:1309-1313

Outcome in Asymptomatic AS Normal Exercise Testing 150 Pts, asymptomatic, AVA<1.0 cm 2, LVEF>50%; Mean age: 69±8 y Lancellotti et al. JACC 59:235 43, 2012

Can exercise stress echocardiography help?

M 75 y, No RF Who is moderatly active AVA 0.65 cm² CASE 1 HR SBP (bpm) (mmhg) Rest 94 133 No symptom Exer 137 154

REST EXERCISE E/E 11 E/E 16 PPG 79 MPG 48 AVA 0.65 cm² PSv 5.1 PPG 119 MPG 89 AVA 0.59 cm² PSv 7.9 EF 64 % EF 71 % Increase in mean pressure gradient = 41 mmhg

Exercise Echo in Asymptomatic AS n=69 asymptomatic severe AS with preserved LV ejection fraction n=26 abnormal exercise test Lancellotti, Piérard Circulation 2005;112:I 377-I 382

Exercise Echo in Asymptomatic AS Truly Asymptomatic Patients MPG + Test AVA Lancellotti et al Circulation 2005 Maréchaux et al, Eur H J 2010; 31,1390 Incremental prognostic value of Exercise Doppler Echo

REST EXERCISE CASE 2 EF 69.9% EF 70.7% F 83 y, Hypertension, Chol, AVA 0.53 cm² TTPG 22 mmhg MPG 74 mmhg AVA 0.53 cm² E/E 22.4 MPG 106 mmhg AVA 0.42 cm² TTPG 68 mmhg E/E 35.5 HR SBP (bpm) (mmhg) Rest 72 128 Exer 120 147 No dyspnea+chest pain Stop for leg discomfort Few VES

PREDICTORS OF AN ABNORMAL EXERCISE RESPONSE 0R MPG diff 1.1 0.0084 Ejection Fraction diff 0.89 0.010 Lancellotti et al Eur J Echo 2008;9:338 p 50 pts with AS <1 cm² Semi-supine exercise test 48% developed symptoms Maréchaux et al Echocardio 2007;24:955

A Year Later: ECHO IN 2008 ++ Decrease in daily activities Exercise intolerance BNP : 636 pg/ml

MPG 81 mmhg AVA 0.44 cm² TTPG 43 mmhg E/E 68

IMPAIRED LONGITUDINAL FUNCTION 17% 2007 12% in 2008

Magne et al. Abstr EACVI, 2014 Courtesy of dr. J Magne

Magne et al. Abstr EACVI, 2014 Courtesy of dr. J Magne

Magne et al. Abstr EACVI, 2014 Courtesy of dr. J Magne

Exercise-induced changes in SPAP Consecutive asymptomatic patients (n=105) with severe AS (AVA<1cm²), preserved LV systolic function (LVEF >55%), normal exercise test Systolic PAP, mmhg 110 100 90 80 70 60 50 40 30 20 10 0 p<0.0001 38±8 Rest 62±1 6 Exercise Prevalence of PHT, % 80 70 60 50 40 30 20 10 0 p<0.0001 6% (n=6) Rest 55% (n=58) Exercise Lancellotti et al. Circulation, 2012 ( 50mmHg) ( 60mmHg)

Cardiac Event-free Survival according to Ex-PHT Cardiac Event-free Survival, % 100 90 80 70 60 50 40 30 20 10 0 81±6% 59±8% 65±6% 55±9% 43±7% p=0.014 27±7% 0 6 12 18 24 30 36 42 48 Follow-up, months 12% of cardiovascular death in Ex-PHT group (vs. 0%) No Ex-PHT Ex-PHT Lancellotti al. Circulation, 2012

Indications for aortic valve replacement in asymptomatic aortic stenosis AVR is indicated in asymptomatic patients with severe AS and systolic LV dysfunction (LVEF < 50%) not due to another cause. AVR is indicated in asymptomatic patients with severe AS and abnormal exercise test showing symptoms on exercise clearly related to AS. AVR should be considered in asymptomatic patients, with normal EF and none of the above mentioned exercise test abnormalities, if the surgical risk is low, and one or more of the following findings is present: very severe AS defined by a peak transvalvular velocity > 5.5 m/s, severe valve calcification and a rate of peak of transvalvular velocity progression 0.3 m/s per year. AVR may be considered in asymptomatic patients with severe AS, normal EF and none of the above mentioned exercise test abnormalities, if surgical risk is low, and one or more of the following findings is present: markedly elevated natriuretic peptide levels confirmed by repeated measurements without other explanations, increase of mean pressure gradient with exercise by > 20 mmhg, excessive LV hypertrophy in the absence of hypertension. Class I I IIa IIb Level C C C C European Heart Journal 2012 - doi:10.1093/eurheartj/ehs109 & European Journal of Cardio-Thoracic Surgery 2012 - doi:10.1093/ejctsezs455).

Factors Highlighted by Exercise Test (Echo) Symptoms LV Dysfunction LV geometry LV Function Severity of VHD PAsP Changes BNP changes Risk Stratification/Outcome Prediction Optimal Timing of Surgery