Asymptomatic Severe Valve Disease Risk Stratification Raphael - - PowerPoint PPT Presentation

Raphael Rosenhek Department of Cardiology Medical University of Vienna

Asymptomatic Severe Valve Disease Risk Stratification

Journées Européennes de la SFC Paris, January 18th 2019

☑ Je n'ai pas de lien d'intérêt potentiel à déclarer Speaker's name : Rosenhek, Raphael, Vienna

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

• r I receive compensation or fees or research grants with a commercial company :

NYHA I-II NYHA III-IV

Years

Tribouilloy C et al. Circulation 1999;99:400

Impact of Preoperative Symptoms on Survival

Timing of Intervention in Mitral Regurgitation

100 80 60 40 20 40 50 60 63 70 80 Survival (%) Age (yrs)

Latent period (increasing obstruction, Myocardial overload) Onset of severe symptoms

angina

Average age of death

2 3 5 Average survival (yrs)

Ross, Braunwald. Circulation 1968

syncope failure

Prognosis of Symptomatic Patients Severe Aortic Stenosis

Exercise-testing Severe „asymptomatic“ Aortic Stenosis

Positive test: symptoms (n=23) BP increase < 20mmHg ST segment depression > 2mm Complex vent. arrhyth.

Amato, MC. Heart 2001;86:381-386

Positive (44 patients) Negative (22 patients)

Time (months)

P=0.0001 1,0 0,8 0,6 0,4 0,2 0 12 24 36 48 60 n=66

Event-free Survival

Role of Exercise-testing Severe Aortic Stenosis

Das, P. Eur Heart J 2005;26:1309-1313 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%

Kang, D.-H. et al. Circulation 2009;119:797-804

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

+ + +

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 No conclusive answer

Kang DH et al. J Am Coll Cardiol 2014;63:2398-2407

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

Suri RM. et al. JAMA 2013;310:609-16 Propensity score matched cohort

6 centers – 24 years (1980-2004) 1021 of 2097 pts without a class I indication for surgery

MIDA: Outcome in Severe Flail MR Early Surgery vs „Watchful Waiting“

Retrospective registry 19% with class II indication (AFib 10%, PHT 11.8%) Watchful Waiting?: „Each patient had follow-up visits with a physician within each participating center or elsewhere“ Arbitrary Cutoff: Early surgery defined as “within 3 months of diagnosis”

Very Severe Aortic Stenosis Early Surgery vs. “Conventional Treatment”

Kang, D. H. et al. Circulation 2010;121:1502-1509 n = 197 AV-Vel ≥ 4.5 m/s mGrad ≥ 50 mmHg AVA ≤ 0.75 cm2

Years

P < 0.001

Surgery 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=0.0018)“

Aortic Stenosis Early Surgery vs. “Conventional Treatment”

Taniguchi et al. The Annals of Thoracic Surgery 2006 82, 2116-2122

Very Severe Aortic Stenosis Early Surgery vs. “Conventional Treatment”

Généreux P et al. J Am Coll Cardiol 2016;67:2263-2288 Metanalysis: All-cause Mortality

Rosenhek, R. et al. N Engl J Med 2000;343:611-617 126 Patients Severe AS (AV-Vel ≥ 4m/s) Asymptomatic Compared to Age-, Gender- Matched General Population Regular Control exams

0 1 2 3 4 5 100 90 80 70 60 50 40 30 20 10

Patients with Aortic Stenosis General Population

Overall Outcome: Wait for Symptoms Strategy

Asymptomatic Severe Aortic Stenosis

P = n.s. Survival (%) Years

Survival - Watchful Waiting Strategy

1 0 2 0 3 0 4 0 5 0 6 0 7 0 8 0 9 0 1 0 0 1 2 3 4 5 6 7 8

Years

All patients

Asymptomatic Severe Mitral Regurgitation

Patients with flail leaflet Expected survival P = n.s. Rosenhek et al. Circulation 2006;113:2238-2244.

Years

1 0 2 0 3 0 4 0 5 0 6 0 7 0 8 0 9 0 1 0 0 1 2 3 4 5 6 7 8

92% 78% 65% 55%

Survival

15 Yr Outcome – Active Surveillance Asymptomatic Severe Mitral Regurgitation

Zilberszac R ... Rosenhek R. JACC CVI 2018;11:1213-1221

Event-Free Survival

n=

AS 866 AR 93 MS 109 MR 367

Age (years) 75 [66-83] 57 [48-69] 56 [44-63] 66 [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 [1.2-3.5] 1.1 [0.8-1.9] 1.1 [0.8-2.5] 1.9 [1.0-3.7]

Characteristics of Operated Patients EORP VHD II 2017

Iung B et al. ESC 2018.

Munt B. et al. Can J Cardiol 2006;22:497-502

All residents of British Columbia on a Waiting List Between 1991 and 2000

Waiting Times for Aortic Stenosis Surgery Assessing Practice

• Risk of Surgery
• Prosth. Complications
• Thromboembolism
• Bleeding
• Endocarditis
• Paravalvular Regurgitation
• Valve Thrombosis
• Need for reoperation
• Late Symptom Reporting
• Risk of death on waiting list
• Higher operative mortality for more

symptomatic pts.

• Risk of sudden death
• Myocardial damage

Risk Benefit

Elective Surgery? Valvular Heart Disease

Modified from Rosenhek, R. et al. Eur Heart J 2002;23:1417-21

Risk Stratification

Mitral Regurgitation Quantification

MR Quantification by Echo and MRI

Lopez-Mattei J. et al. Am J Cardiol 2016;117:264-270 Regurgitant Fraction Regurgitant Volume

Antoine C et al. Circulation 2018;138:1317-1326

Survival in Mitral Regurgitation Severity of MR

Velocity vs. Valve Area Natural History

Minners, J. et al. Eur Heart J 2008 29:1043-1048

AVA < 1 cm2 Sensitive AV-Vel ≥ 4.0 m/s Specific

Rusinaru D et al JACC Cardiovascular Imaging, Volume 8, Issue 7, 2015, 766–775

Dimensionless Index Aortic Stenosis Quantification

TVILVOT/TVIAV 488 patients with preserved (≥50%) ejection fraction and no or minimal subjective symptoms, diagnosed with ≥ mild AS

Rosenhek R et al. Eur Heart J 2004;25:199-205

Severity of Aortic Stenosis Natural History

Years Event-free Survival (%)

P < 0.0001

AV-Vel ≥ 5.5 m/s AV-Vel 4.0 to 5.0 m/s AV-Vel 5.0 to 5.5 m/s AV-Vel 3.0 to 4.0 m/s AV-Vel 2.5 to 3.0 m/s

Rosenhek R et al. N Engl J Med 2000;343:611-617 Rosenhek R et al. Circulation 2010;121:151-156 64 mmHg 100 mmHg 121 mmHg

Life Expectancy in Years

Europe and US

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

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

Event-free Survival

30% impaired Mobility 9 cardiac deaths

Zilberszac R et al. J Am Coll Cardiol Cardiovasc Imaging 2017;10:43-50

10 20 30 40 50 60 70 80 90 100 1 2 3 4

Event-free Survival (%) Years

P = 0.84 Age 70-80 years Age ≥ 80 years P = 0.84

10 20 30 40 50 60 70 80 90 100 1 2 3 4

Years

P = 0.84

AV-Vel 4-5 m/s AV-Vel ≥ 5 m/s P < 0.001

Severe Asympt AS in the Elderly ≥ 70 yrs

Ventricular Response

Aortic Stenosis

Lindman B et al. Nat Rev Dis Primers. 2016;2:1-28.

Patients with moderate or severe aortic valve calcification and aortic jet velocity increase > 0.3 m/s within 12 months Time from observation

• f rapid progression (days)

Event-free Survival (%)

Rosenhek, R. et al. N Engl J Med 2000;343:611-617

100 90 80 70 60 50 40 30 20 10 0 1 2 3 4 5

2 year event-rate: 80%

Valve Calcification and Rapid Progression Severe Aortic Stenosis

Aortic Stenosis Survival: BNPratio

Clavel MA et al. J Am Col Cardiol 2014;63:2016-25

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

Midwall Fibrosis Aortic Stenosis - MRI

Surgery in Severe Aortic Stenosis

Evolution of the Guidelines

ACC/AHA

1998

ESC

2002

ACC/AHA

2006

ESC

2007

ACC/AHA

2008

ESC/EACTS

2012

ACC/AHA

2014

ESC/EACTS

2017 Symptoms I I I I I I I I Symptoms during exercise testing IIa IIb I IIb I I I LVEF < 50%

IIa IIa I I I I I I

Undergoing other cardiac surgery I I I I I I I I Very severe AS (ESC 5.5 m/s, ACC 5.0 m/s) IIb IIb IIa IIa IIa Exercise test: Blood pressure drop IIa IIa IIb IIa IIb IIa IIa IIa Calcified valve + rapid progression

(≥ 0.3 m/s/yr)

IIa IIb IIa IIb IIa IIb IIa Elevated BNP (3x age/gender corrected) IIb IIa Severe pulmonary hypertension

(sPAP > 60mmHg)

IIa Exercise echo: ↗mGrad ≥ 20 mmHg IIb Excessive LVH – no hypertension IIb IIb IIb

Ventricular Arrhythmias

IIb IIb

Asymptomatic / SAVR

20 40 60 80 100 2 4 6 8 10

Timing of Intervention in Mitral Regurgitation

Enriquez-Sarano et al. Circulation 1994;90:830-837.

Impact of Preoperative EF on Survival

73% EF ≥ 60% 53% EF 50-60% 32% EF <50%

• NYHA I: 45 (11%)
• NYHA II: 86 (21%)
• NYHA III: 213 (52%)
• NYHA IV: 65 (16%)

Risk Stratification in Mitral Regurgitation Atrial Fibrillation & Pulmonary Hypertension

Le Tourneau et al. Heart 2010;96:1311-1317

Years

* 37% in NYHA classes III and IV

Postoperative survival

STS database 14604 mitral repair procedures 1991-2007

Badhwar et al. Ann Thor Surg 2012;94:1870-1877

Risk Stratification in Asymptomatic MR Event-free Survival: LA-Size

Le Tourneau T. et al. J Am Coll Cardiol 2010;56:570-8

Surgery in Severe Primary MR

Evolution of the Guidelines

ACC/AHA

1998

ESC

200 2

ACC/AHA

2006

ESC

2007

ACC/AHA

2008

ESC

2012

ACC/AHA

2017

ESC/EACTS

2017 Symptoms I I I I I I I I Asymptomatic with LVEF 30 - 60% I I I I I I I I Asympt with dilated LV (LVESD mm)

45 45 40 45 40 45/40 40 45

Progressive LV dil or decrease in EF IIa Afib or sPAP ≥ 50 mmHg IIa IIa IIa IIa IIa IIa IIa IIa

Surgery should be considered in asymptomatic patients with preserved LVEF (>60%) and LVESD 40–44 mm* when a durable repair

is likely, surgical risk is low, the repair is performed in heart valve centres, and at least

• ne of the following findings is present:
• flail leaflet or,
• presence of significant LA dilatation (volume index ≥60 mL/m²

BSA) in sinus rhythm.

IIa

Likelihood of successful and durable repair >95% without residual MR and expected mortality <1% (Heart Valve Center of Excellence)

IIa

Dilated left atrium (≥ 60 ml/m2) or sPAP ≥ 60mmHg on exercise (low surgical risk and high likelihood of repair)

IIb

Asympt (LVESD < 45 mm, LVEF ≥ 60%)

Gammie JS et al. Circulation 2007;115:881-887

Timing of Intervention in Mitral Regurgitation Influence of Hospital Procedural Volume

2 4 6 8 10 12 14 16

1 to 35 35 to 70 71 to 140 140+

Adverse Outcomes (%)

Procedural Volume

Bolling S et al. Ann Thorac Surg 2010;90:1904-11

Mitral Valve Repair in Mitral Regurgitation

Surgeon Volume and Repair Rate

Proportion repaired # of isolated mitral cases per surgeon and year

Median number

• f surgeries: 5 !!

Holzhey D et al. Circulation 2013;128:483-491

Mitral Valve Repair

Individual Surgeon Experience

Severe Complications Mortality

Valve Clinic Impact – Vienna Experience

P < 0.001

50 100 150 200 250 300 350 400 Ini al Symptoma c Presenta on Enrolled in a Follow-up program Symptom repor ng at scheduled visit Symptom repor ng before scheduled visit

Days to symptom reporting P < 0.001

Symptom Reporting in Aortic Stenosis

79% 21%

Zilberszac R et al. Eur Heart J Cardiovasc Imaging 2017;18:138-144.

High-Quality Care in Valve Disease

Integrative Approach Concept of Valve Centers

Interventional Risk Postinterventional Outcome Need for Reintervention Natural History Life Expectancy Individual Risk Imaging Disease Severity Anatomy

Heart Team

Timing and Choice of Procedure

Adapted from Rosenhek R et al. Eur Heart J 2012;33:822-828

• Multidisciplinary Teams
• Volume
• Quality Assessment (robust audit)
• Excellence in

Imaging Intervention Surgery Modified from Chambers J et al. Eur Heart J 2017;38:2177-2183. Lancellotti P et al. Eur Heart J 2013;24:1597-1606

Heart Valve Clinics