results from >2,300 patients in the source tavi registry: changes in patient populations with...

Results from >2,300 Patients in The SOURCE TAVI Registry: Changes in

Patient Populations with time.

Dr Martyn Thomas on behalf of the SOURCE investigators.

Clinical Director, Cardiovascular Services

St Thomas’ Hospital

Kings Health Partner’s

London

Disclosure Statement of Financial Interest

• Grant/Research Support• Consulting Fees/Honoraria

• Edwards Lifesciences• Boston Scientific• Cordis

Within the past 12 months, I or my spouse/partner have had a financial interest/arrangement or affiliation with the organization(s) listed below.

Affiliation/Financial Relationship Company

Background:THE SOURCE Registry describes the outcomes in the first group of TAVI patients treated with the Edwards SAPIEN Valve in Europe.

COHORT 1:Nov 07 to Jan 0934 Centres with 1123 patients

The SOURCE Registry has: 100% procedure data

30D Data: COH1 – 99.9% | COH2 – 98%1Yr Data: COH1 – 98% | COH2 – Avail 2011

All consecutively enrolled

Excluded: 2 Centres / 85 patients• Unable to obtain Ethic Cte approval or

administrative issues.

3Data Extract – 17MAY2010, 30JUL2010

32 Centres with 1038 patients

COHORT 2: Feb 09 to Dec 0940 Centres with 1306 patients

TOTAL:

38 Centres with 2344 patients

=

2 Centres• Elected not to participate. –

–

+

=

Methods:Consecutive Patients

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• The current data is from centres who could provide data on 100% of their consecutively treated patients during this time.

• Centres that could not provide this were excluded.

• Transfemoral, Transapical, and [(trans-axillary & trans-aortic)=5] cases are included in this consecutive series.

• The SOURCE Registry used the 23mm and 26mm Edwards SAPIEN THV requiring 22/24F Transfemoral sheaths and 26F Transapical sheaths.

Methods

• This is a clinical registry. All events and values are site reported and there are no core labs.

• The SOURCE Registry Principal Investigators reviewed and adjudicated all clinical and adverse events reported into the Medidata Rave Database.

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Site Name Pts Site Name PtsKarlsruhe/Städisches Klinikum + Herzklinik – G Schymik, H Schroefel 204 Frankfurt/Uniklinik – V Schächinger, M Doss 50

Leipzig/Herzzentrum – T Walther, G Schuler 162 Zurich/KlinikimPark + Hirslanden – W Amann, F Bernet 50London/St Thomas’ + King’s – M Thomas, O Wendler 149 Lund/Universitetssjukhuset – G Olivecrona, P Johnsson 42Milan/Monzino – P Bigliogli, M Fusari 113 Jena/Uniklinik – K Hekmat, M Ferrari 39Hamburg/Uniklink – H Treede, O Franzen 109 Leiden/ – M Schalij, A de Weger 37Munich/DHZ – R Lange 106 A Coruna/ – N Vazquez, J Cuenca 36Paris/Bichat – D Himbert, P Nataf 98 Paris/HEGP – D Blanchard, JN Fabiani 34Mercogliano/Clinica Montevergine – P Rubino, G Sorrogpago 91 Leuven/Gasthuisberg – C Dubois, P Herijgers 32

Massy/Jacques Cartier – T Lefèvre, M Romano 84 Lübeck/Uniklinik – ED Kraatz, H Sier 30Essen/Uniklinik – H Eggebrecht, M Thielmann 82 Torino/ – I Sheiban, M Rinaldi 30Münster – H Baumgartner, H Reinecke 80 Padova/ – G Isabella, G Gerosa 28Madrid/S Carlos – C Macaya, E Rodriguez 79 Innsbruck/Uniklinik – L Mueller, T Bartel 26Milan/S Raff – I Michev, F Maisano 79 Cambridge/Papworth – C Densem, P Calvert 22Aarhus/Skejby – HR Andersen, KE Klaaborg 71 Utrecht/ – P Stella, J Kluin 19Rouen/CHU – H Eltchaninoff, JP Bessou 66 Barcelona/ – J Angel, A Igual, 17Bern/Inselspital – P Wenaweser, T Carrel 60 Tampere/ – P Kosonen, M Kohonen 15Bruxelles/St Luc – P Astarci, J Kefer 59 Vigo/ – A Inigues, G Pradas 14Athens/Onassis – K Spargias, G Stavridis 55 London/Brompton – M Mullen, N Moat 13San Sebastian/Gipuzkoa – J Goiti, M Larman 53 University of Hradec Kralove/ – J Stasek, J Vojacek 10

TOTAL 2344

The SOURCE Registry – Total Enrollment


The Logistic EuroSCORE overestimates but does categorise risk

Don’t dismiss the value of EuroSCORE to categorise risk

Patient Groupings of Interest in theSOURCE Registry

Hypothesis: Patient indication may have changed over the time course of the SOURCE registry.

• Log EuroSCORE >20 (“standard risk”)• Log EuroSCORE <20 (usually patients with

risk factors not captured by Log EuroSCORE – potentially “lower risk”……..but unclear)

• Other patients including “Valve in Valve” to treat degenerative aortic bioprosthesis.

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Changes in patient groups with time(Numbers of patients per category)

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Patient Number / Percentage

CategoryCohort 1 (N=1038)

Cohort 2 (N=1306)

P-Value

Log EuroSCORE >20 695 / 66.9% 734 / 56.2% <.0001 Log EuroSCORE < 20 340 / 32.8% 568 / 43.5% <.0001

Data Extract – 17MAY2010, 30JUL2010


Cohort 2 (N=1306)

P-Value

Mean Log EuroSCORE 27.6 ± 15.5 25.5 ± 21.9 0.0079


Cohort 2 (N=1306)

P-Value

SAPIEN in prior aortic bioprosthesis

2 / 0.2% 26 / 1.9% <.0001

(4 patients included in database outside Cohort 1 and Cohort 2 have been excluded)This was not anticipated!!

Has the different patient population resulted in a change in 30 day survival?


Cohort 1 Cohort 2

30 day survival 91.2% 89.9%

30 Day Survival: “standard risk”Cohort 1 vs. Cohort 2 with ES>20


Category Cohort 1 (N=1038) Cohort 2 (N=1306) P-Value

Log EuroSCORE >20 695 / 66.9% 734 / 56.2% <.0001


Survival

Category Cohort 1 (N=1038) Cohort 2 (N=1306) All (N=2344) P-Value

Log EuroSCORE >20 90.1% 88.2% 89.1% 0.2504

30 Day Survival: Cohort 1 vs. Cohort 2 with ES<20


Category Cohort 1 (N=1038) Cohort 2 (N=1306) P-Value

Log EuroSCORE <20 340 / 32.8% 568 / 43.5% <.0001


Survival Category Cohort 1 (N=1038) Cohort 2 (N=1306) All (N=2344) P-Value

Log EuroSCORE <20 94.1% 92.7% 93.3% 0.4272

Demographics and Risk Factors – Overall Group <20 & >20Why TAVI for <20?


Risk FactorAll Treatments < 20

(N=908)All Treatments >= 20

(N=1429)All Treatments p-

valueNYHA Class IV 83 ( 9.14%) 244 (17.07%) <.0001

Female 523 (57.60%) 815 (57.03%) 0.6345

Age >= 80 Years 526 (57.93%) 1016 (71.10%) <.0001

Smoking 207 (22.80%) 263 (18.40%) 0.0110

Coronary Artery Disease 396 (43.61%) 838 (58.64%) <.0001

Congestive Heart Failure 218 (24.01%) 499 (34.92%) <.0001

Myocardial Infarction 99 (10.90%) 262 (18.33%) <.0001

Carotid artery stenosis (over 50%) 63 ( 6.94%) 218 (15.26%) <.0001

Porcelain Aorta 91 (10.02%) 95 ( 6.65%) 0.0037

Mitral valve disease 260 (28.63%) 448 (31.35%) 0.1803

Cancer 182 (20.04%) 186 (13.02%) <.0001

Pulmonary disease 206 (22.69%) 389 (27.22%) 0.0149

Pulmonary disease: FEV1 less than 1.0 32 ( 3.52%) 29 ( 2.03%) 0.0327

Renal insufficiency / Failure 195 (21.48%) 476 (33.31%) <.0001

Post thoracic radiation therapy 14 ( 1.54%) 6 ( 0.42%) 0.0396

Peripheral vascular disease (non carotid) 123 (13.55%) 346 (24.21%) <.0001

PTCA / stent 203 (22.36%) 420 (29.39%) 0.0002

CABG 108 (11.89%) 392 (27.43%) <.0001

Carotid endarterectomy / Carotid stent 20 ( 2.20%) 70 ( 4.90%) 0.0009

Prior surgical aortic bioprosthesis in place? (VIV) 6 ( 0.66%) 20 ( 1.40%) 0.0166

“Frailty” not measuredin the SOURCE database

Comparison of <20 patient demographics and risk factors in Cohort 1 and 2: Has the pattern of risk

changed?


Comorbidity / Risk FactorCohort 1(N=340)

Cohort 2(N=568)

P-Value by Cohort

Female 192 ( 56.47%) 331 ( 58.27%) 0.6273

Coronary Artery Disease 141 ( 41.47%) 255 ( 44.89%) 0.3333

Congestive Heart Failure 60 ( 17.65%) 158 ( 27.82%) 0.0005

Carotid artery stenosis (over 50%) 24 ( 7.06%) 39 ( 6.87%) 0.8937

Porcelain Aorta 38 ( 11.18%) 53 ( 9.33%) 0.4242

Mitral valve disease 68 ( 20.00%) 192 ( 33.80%) <.0001

Pulmonary disease 82 ( 24.12%) 124 ( 21.83%) 0.4613

Renal insufficiency / Failure 62 ( 18.24%) 133 ( 23.42%) 0.0669

Peripheral vascular disease (non carotid) 49 ( 14.41%) 74 ( 13.03%) 0.5497

CABG 43 ( 12.65%) 65 ( 11.44%) 0.5976

“True risk” in Cohort 2 may have gone “up”.

1 Year Kaplan Meier Survival: when is Euroscore reflected in survival benefit?

Cohort 1 – ES <20 vs. >20


P=0.0529

Cohort 1 ES<20 ES>20

1 year survival 79.7% 74.2%

“Valve in valve”: an indication for TAVI?

• In The SOURCE Registry trans-catheter valve therapy appears to be an emerging indication for the treatment of a failing surgical aortic bioprosthesis.

• Can we categorise these patients?

• Is there “gold standard” surgical data for redo surgery?

“Valve In Valve” Patient DemographicsTHE SOURCE Registry


Risk Factor

Total Prior Surgical Bioprosthesis

(N=28)

Age 78.73 + 6.99

Female 12 (46.15%)

EuroSCORE 34.06

Peripheral vascular disease (non carotid) 6 (23.08%)

Coronary Artery Disease 11 (42.31%)

Congestive Heart Failure 8 (30.77%)

Myocardial Infarction 6 (23.08%)

Mitral valve disease 12 (46.15%)

PTCA / stent 6 (23.08%)

CABG 7 (26.92%)

VERY HIGH RISK GROUP OF PATIENTS

26/28 TAapproach

Surgical redo AVRPatient Demographics

Contemporary Surgical literature is limited

Age 56

Ejection Fraction 57%

Age 63.5

Ejection fraction 58%

Perioperative Risk of Redo Aortic Valve ReplacementAnn Thorac Cardiovasc Surg 2009Christiansen et al

Operative risk of reoperative aortic valve replacementJ Thorac Cardiovasc Surg 2005Potter et al

Appears “low risk” patient population

Age 56

Ejection Fraction 53%Reoperative surgery for degenerated aortic bioprostheses: predictors for

emergencySurgery and reoperative mortality: Vogt et al

Eur J Cardiothoarac Surg 2000

Risk factors for operative mortality of repeat heart surgery.

Repeat heart valve surgery: Risk factors for operative mortality.J Thorac Cardiovasc Surg 2001Jones et al

• Factors associated with operative mortality

- age

- associated coronary bypass grafting

- valve thrombosis or endocarditis

- replacement of mechanical heart valve

Mean age 54.7yrs

Risk factors for operative mortality of repeat heart surgery.

Risk Factor Operative Mortality

Gender MaleFemale

4.6%13.3%

Age at reop <6060-70>70

0%8.5%12.6%

Ejection Fraction > 50%< 50%

6.5%15.4%

NYHA class I/IIIIIIV

2.0%4.2%16.0%

Predictive risk factors of re-operative AVR mortality

Re-operation for bioprosthetic aortic structural failure – risk assessment.Jamieson et al. Eur J Cardiothorac Surgery 2003

The SOURCE Registry: “Valve in Valve”What valves have been treated? Where next?

• Previous bioprostheses include Carpentier Edwards, Hancock, Mitraflow and Mosaic (21-25mm valves).

• This patient population was not anticipated at the outset of the SOURCE registry.

• Careful data collection planned for this group in the SOURCE XT registry.

• Because the patient populations undergoing surgical redo AVR and trans-catheter treatment appear so different it will be difficult to compare outcomes. Ideally a randomised trial would resolve this but patient numbers are now relatively small.

Changes in Patient Populations with time:CONCLUSIONS 1

• There has been a change in the patient population of TAVI patients between Cohort 1 and Cohort 2 of the SOURCE Registry.

• This is reflected by an increased number of patients with a Log EuroSCORE of <20 in Cohort 2. However the true “risk” of Cohort 2 may well have gone up, reflected by increased patients with heart failure and mitral regurgitation. 30 day outcomes for Cohort 1 and 2 are the same.

• Urgent need for the development of “TAVI risk score” to include other factors ie. Frailty; as EuroSCORE may not be truly assessing “risk”.

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Changes in Patient Populations with time:CONCLUSIONS 2

• “Valve in valve” appears an emerging indication for

TAVI.• The “valve in valve” patients in SOURCE are very

high risk.• The contemporary data for redo surgical AVR as a

comparator is limited but does suggest a completely different patient population.

• Comparison of these two treatment options will be

difficult in the absence of randomised data.

results from >2,300 patients in the source tavi registry: changes in patient populations with...

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