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
CoreValve ADVANCE II Study 4
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
CoreValve ADVANCE II Study 5
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
CoreValve ADVANCE II Study 6
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
CoreValve ADVANCE II Study 7
†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
CoreValve ADVANCE II Study 8
†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.
Permanent Pacemaker Rate at 30 Days
CoreValve ADVANCE II Study 9
†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.
Permanent Pacemaker Rate at 6 Months
CoreValve ADVANCE II Study 10
• 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
CoreValve ADVANCE II Study 13†McNemar’s test on paired data
Valve Performance
CoreValve ADVANCE II Study 14
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
CoreValve ADVANCE II Study 17
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
CoreValve ADVANCE II Study 19
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
CoreValve ADVANCE II Study 20
Patient Disposition
CoreValve ADVANCE II Study 21
Timing of Permanent Pacemaker Implantation
CoreValve ADVANCE II Study 22
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
CoreValve ADVANCE II Study 24†McNemar’s test on paired data
†Calculated from paired baseline and 6 month values, N=66
Left Ventricular Mass
CoreValve ADVANCE II Study 25
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