georg nickenig, universitatsklinikum bonn, germany jan-malte sinning, universitatsklinikum bonn,...

Georg Nickenig, Universitatsklinikum Bonn, Germany

Jan-Malte Sinning, Universitatsklinikum Bonn, Germany

Jan Kovac, Glenfield Hospital, Leicester, UK

Peter de Jaegere, Erasmus MC, Rotterdam, NL

Anna-Sonia Petronio, Azienda Ospedaliero Universitaria Pisana, Italy

(On Behalf of the ADVANCE II Investigators)

Six-Month Performance of a Self-Expanding Valve in a Study of Best Implantation Practices:The CoreValve ADVANCE II Study

• Accumulating clinical experience has led to the development of best-practice recommendations aimed at improving the results of the transcatheter aortic valve implantation (TAVI) procedure with the CoreValve system.

• These recommendations include:Patient screening and valve size selection using multislice

computed tomographycontrol of implant depth to 6 mm or less relative to the

aortic annulusadherence to international guidelines to determine the

need for post-TAVI permanent pacemaker implantation

Background

CoreValve ADVANCE II Study 2

Study Design

Purpose• To implement best practices for CoreValve deployment and

apply rigorous data collection and core laboratory analysis to assess outcomes

Design • Prospective, non-randomized, multicenter, observational study• Follow-up at 7 days, 1 month, and 6 months

Device • CoreValve 23, 26, 29, and 31 mm• Transfemoral, subclavian, and direct aortic routes

Core Labs • MSCT, angiography (implant depth), ECG, pacemaker interrogation, and echo

Event Adjudication

• Adverse events according to VARC-2 by independent CEC• Permanent pacemaker indications to 2007 ESC guidelines by

independent adverse event advisory committeeCoreValve ADVANCE II Study 3

Hospital Principal Investigator Enrollment

Universitätsklinikum Bonn Bonn, DE Prof. Dr. med. G. Nickenig

40

Erasmus MC Rotterdam, NL Prof. P. de Jaegere 40

Azienda Ospedaliero Universitaria Pisana

Pisa, IT Prof. ssa S. Petronio 35

Universitätsklinikum Heidelberg Heidelberg, DE Prof. Dr. med. R. Bekeredjian

22

University Hospital Antwerp Antwerp, BE Prof J. Bosmans 19

Istituto Clinico S. Ambrogio Milan, IT Prof. F. Bedogni 16

Cardiocenter Hospital Podlesi Třinec, CZ Dr. M. Branny 12

Charite, Campus Mitte – Kardiologie Berlin, DE Prof. Dr. med. K. Stangl 8

Glenfield Hospital Leicester, UK Dr. J. Kovac 8


Participating Centers

Key Inclusion and Exclusion Criteria

Inclusion

• Symptomatic aortic valve stenosis• AVA <1.0 cm2 (or AVA index <0.6 cm2/m2) plus either mean pressure

gradient >40 mmHg or jet velocity >4 m/s• High risk for surgical AVR as determined by local heart teams• Aortic annulus diameter 18-29 mm

Exclusion• Pre-existing device which regulated heart rhythm• Pre-existing class I or II indication for permanent pacemaker• Persistent and permanent atrial fibrillation

• Paroxysmal AF was not an exclusion criteria

Purposeful patient selection to allow study of new conduction disturbances specifically due to TAVI


Medical history (N=200) % or mean ± SD Conduction (core lab, N=200) % or mean ± SD

Age (yrs.) 80.2 ± 6.7 PQ interval (msec, mean ± SD ) 186.6 ± 39.3

Male 47.5 AV conduction

Log EuroSCORE II 9.0 ± 8.9 Normal 75.8

STS 7.2 ± 6.8 1st degree AV block 24.2

NYHA III / IV 74.4 IV conduction

CAD 60.3 Normal 76.8

PVD 27.6 LBBB 5.6

Cerebrovascular disease 15.2 RBBB 6.1

History of AF 10.5 LAFB 10.6

Prior MI 15.1 LPFB 0.5

Prior PCI 30.8

Prior CABG 15.6

COPD 21.1

Permanent pacemaker** 0.5

**One patient received a PPM after providing consent, but before the index procedure

Baseline Characteristics


1 Month 6 Months

(n)†Rate*

(%) (n)†Rate*

(%)

All-cause mortality 3 1.6 17 9.2

Cardiovascular mortality 3 1.6 10 5.3

Stroke 4 2.1 5 2.6

Major stroke 2 1.0 3 1.6

Life-threatening or disabling bleeding 8 4.1 10 5.4

Major bleeding 23 11.9 24 12.4

Major vascular complications 23 11.9 23 11.9

Myocardial infarction 1 0.5 3 1.7

Acute kidney injury, stage III 1 0.5 1 0.5

*Kaplan-Meier event rate†We only consider the first event in each complication category for a given patient

Safety outcomes


†Kaplan-Meier ratesImplant depth defined as the maximal distance between the intraventricular end of the bioprosthesis and the aortic annulus at the level of the non-coronary cusp, as measured by angiography in the projection chosen for deployment. Assessed by core laboratory.

Primary Endpoint

When CoreValve was deployed according to best practices, the resulting permanent pacemaker rate was 13.3% at 1 month



Permanent Pacemaker Rate at 30 Days



Permanent Pacemaker Rate at 6 Months


• Intrinsic rhythm was determined by temporary VVI programming at 30 bpm• 25 patients had data available at day 7 and 6 months for paired analysis

Intrinsic Rhythm in Patients with Pacemakers

CoreValve ADVANCE II Study 11†McNemar’s test on paired data

Paired data showed that the amount of time ventricles were paced during the follow-up period decreased significantly from day 7 to 6 months (p=0.03†)

Ventricular Pacing

CoreValve ADVANCE II Study 12†Signed Rank test comparing 7 day % ventricular pacing with 6 months for the 19 patients with paired data

• New-onset Left Bundle Branch Block (LBBB) resolved with time• Paired data showed 36.4% had resolved spontaneously by 6 months• Patients with permanent pacemakers were excluded from this analysis

Resolution of Left Bundle Branch Block


Valve Performance


More than mild PVL decreased significantly over time (p=0.022†)

Paravalvular Leak

CoreValve ADVANCE II Study 15†GEE logistic regression model for the odds of moderate/severe PVL over time using all available data at 7 days, 1 month, and 6 months

MR (≥ mild) decreased significantly over time (p=0.04†)

Mitral Regurgitation

CoreValve ADVANCE II Study 16†GEE logistic regression model for the odds of more than mild MR over time using all available data at baseline, 7 days, 1 month, and 6 months

†Calculated from paired baseline and 6 month values, N=66

Wall Thickness


The proportion of subjects with LVEF ≥45% increased significantly over time (p=0.009†)

Left Ventricular Ejection Fraction

CoreValve ADVANCE II Study 18†GEE logistic regression model for the odds of LVEF >45% over time using all available data at baseline, 7 days, 1 month, and 6 months

TCT 2013 LBCT

NYHA Functional Status


Adherence to best clinical practices during CoreValve implant leads to the following 6-month outcomes:

• All-Cause Mortality = 9.2%• All Stroke = 2.6%• Pacemaker implantation rate = 14.5% for class I / II indications at ≤6 mm,

25.7% overall in patients with known implant depths (N=192/194)• Spontaneous recovery from LBBB in 36.4% of patients• Acute improvement in aortic valve hemodynamics with a trend of continued

improvement with time• Low post-procedural rate of moderate / severe PVL which decreased

significantly to 4.3% • Reverse cardiac remodeling • Relief of heart failure symptoms

Summary


Patient Disposition


Timing of Permanent Pacemaker Implantation


43 / 50 (86%) of pacemakers were implanted within the first month of TAVI

Valve Performance

CoreValve ADVANCE II Study 23†t-test from paired day 7 and 6 month values

Paired data show more than mild PVL decreased significantly from day 7 to 6 months (p=0.005†)

Paravalvular Leak | Paired Analysis


†Calculated from paired baseline and 6 month values, N=66

Left Ventricular Mass


Permanent Pacemaker Implant (PPI) status did not impact LVEF over time (p=0.74†)

Left Ventricular Ejection Fraction

CoreValve ADVANCE II Study 26†GEE logistic regression model for the group effect, indicating if LVEF differs between pacemaker groups across time using all available data at baseline, 7 days, 1 month, and 6 months

georg nickenig, universitatsklinikum bonn, germany jan-malte sinning, universitatsklinikum bonn,...

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