Leonardo da Vinci Figure 6. Spirals in art: (1) the drawings of Leonardo da Vinci from Vindzone Library showing spiral flows in the heart cavity.3
La Bockeria et al. European Journal Cardio-thoracic Surgery 2006;295:S251 – S258 3
Enhanced left ventricular mass regression after aortic valve replacement in patients with aortic stenosis is associated with Ayyazimproved Ali, Amit Patel,long-term Ziad Ali, Yasirsurvival Abu-Omar, Amber Saeed, Thanos Athanasiou and John Pepper J Thorac Cardiovasc Surg 2011; 142:285-291 DOI: 10.1016/j.jtcvs.2010.08.084
Plastic Casts of the Left Ventricle Figure 8. Plastic casts of the left ventricle (A. Gorodkov): (1) normal; (2) dilated‌3
3
La Bockeria et al. European Journal Cardio-thoracic Surgery 2006;295:S251 – S258
Francisoco (Paco) Torrent-Guasp Figure 1. Francisco (Paco) Torrent-Guasp.2
Editorital. Torrent-Guasp’s anatomical legacy. European Journal Cardio-thoracic Surgery 2006;295:S18-S20 2
Spiral Flow: unfolding the heart Figure 22. Unscrolling of the myocardial band.
G.D. Buckberg et al. / European Journal of Cardio-thoracic Surgery 29S (2006) S75-S97
Ventricular Rotation Figure 8. Ventricular rotation.1
1
C. Coghlan et al. European Journal Cardio-thoracic Surgery 2006;295:S4-S17
Spiral Flow Figure 4. Right-handed helical flow in the ascending aorta and arch during mid and late systole.
Markl M, Draney MT, Miller DC, et al. J Thorac Cardiovasc Surg 2005;130:456-63
Spiral Flow
Kilner, et al. Circulation 1993;88 [part 1]: 2235-2247
Sinus Circulation
Kilner, et al. Circulation 1993;88 [part 1]: 2235-2247
Spiral Laminar Flow: An Examination of this critical blood flow pattern and the early results of a first in man study. F Vermassen1, J Dick2, JG Houston2, PA Stonebridge2 1 Department of Vascular Surgery, Universitair Ziekenhuis, Ghent 2 Vascular Unit, Tayside University Hospitals Trust, Dund ee
Figure 1. Detecting spiral laminar flow
Figure 2. Characteristic spiral flow pattern in healthy arteries
Non spiral and spiral (helical) flow patterns in stenoses: in vitro observations using spin and gradient echo magnetic resonance imaging (MRI) and computational fluid dynamic modelling. Stonebridge PA, Buckley C, Thompson A, Dick J, Hunter G, Chudek JA, Houston JG, Belch JJ. Int Angiol. 2004 Sep;23(3):276-83.
PROACT Update Status as of Jan. 1, 2013
Enrollment by Group
As of 1/1/2013
– slide 112
AVR High Risk Group Postrandomization Events Event
Major Bleed Minor Bleed Total Bleed
Control (ptyr=675.3) (2.0 – 3.0) N Rate (%/ptyr) 22 3.26 23 3.41 45 6.66
Test (ptyr=606.4) (1.5 – 2.0) N Rate (%/ptyr) 9 1.48 8 1.32 17 2.80
Rate Ratio
95% CI
P-value
0.46 0.39 0.42
0.21-0.99 0.17-0.87 0.24-0.73
0.047 0.021 0.002
(test/control)
Stroke TIA Neurologic Event
3 5 8
0.44 0.74 1.18
5 7 12
0.82 1.15 1.98
1.86 1.56 1.67
0.44-7.77 0.49-4.91 0.68-4.09
0.397 0.448 0.261
Peripheral TE Thrombosis
1 1
0.15 0.15
3 2
0.49 0.33
3.34 2.23
0.35-32.11 0.20-24.56
0.296 0.513
Major Event (Major bleed, stroke, thrombosis) All Above Events
26
3.85
16
2.64
0.69
0.37-1.28
0.234
55
8.14
34
5.61
0.69
0.45-1.06
0.087
Sudden Death Valve-related death
1 1
0.15 0.15
3 2
0.49 0.33
3.34 2.23
0.35-32.11 0.20-24.56
0.296 0.513
Total Mortality
9
1.33
10
1.65
1.24
0.50-3.04
0.643
MVR Group Postrandomization Events Event
Major Bleed Minor Bleed Total Bleed
Control (ptyr=120.2) (2.5 – 3.5) N Rate (%/ptyr) 8 6.66 6 4.99 14 11.65
Test (ptyr=102.8) (2.0 – 2.5) N Rate (%/ptyr) 7 6.81 1 0.97 8 7.78
95% CI
Pvalue
0.98 5.13 1.50
0.31-3.17 0.62-236 0.59-4.12
0.965 0.091 0.360
Rate Ratio (control/test)
Stroke TIA Neurologic Event
4 3 7
3.33 2.50 5.82
1 2 3
0.97 1.95 2.92
3.42 1.28 2.00
0.34-168.5 0.15-15.36 0.46-11.96
0.242 0.784 0.307
Peripheral TE Thrombosis
0 1
0.00 0.83
0 1
0.00 0.97
NA 0.86
NA 0.01-67.13
NA 0.912
Major Event (Major bleed, stroke, thrombosis) All Above Events
13
10.81
9
8.75
1.24
0.49-3.27
0.625
22
18.30
12
11.67
1.57
0.74-3.48
0.206
Sudden Death Valve-related death Total Mortality
0 0
0.00 0.00
1 1
0.97 0.97
NA NA
NA NA
0.278 0.278
1
0.83
2
1.95
0.43
0.01-8.21
0.475
Relationship of TE to Bleed
Summary • AVR High Risk – Hypothesis proven • Non-inferior treatment group • Treatment group meets FDA events criteria (OPC) • In fact, treatment group superior in bleeding event rates. – Application submitted to FDA – Abstract submitted to AATS and accepted • Article and other abstracts to follow
• Follow-up still to short in low risk AVR and MVR for conclusions – Early MVR returns encouraging – Enrollment should close shortly
Proposed Label Change •
•
Anticoagulation – Patients with On-X® valves should be maintained on long-term warfarin anticoagulation to maintain an International Normalized Ratio (INR) of 1.5 – 2.0 for aortic valve replacement patients and 2.5 – 3.5 for mitral or multiple valve replacement patients. The addition of 81 mg/day of aspirin is also recommended for aortic valve patients able to tolerate aspirin. CAUTION – Studies show stable control of INR provides better clinical results. Also studies show that patients should be regularly monitored and have dose adjustments to avoid INR’s lower than 1.5 or higher than 2.5 for aortic valve patients, as values outside this range are associated with increased risk of adverse events.
Enrollment by Center Center
Total
Current Month
Center
Total
Current Month
Tacoma General, Tacoma
205
3
Forsyth, Winston-Salem
16
1
St. Francis, Indianapolis
88
3
Mary Washington, Fredericksburg
16
1
Maine Medical, Portland, ME
80
3
Beth Israel Deaconess, Boston
15
0
Tucson VA, Tucson
71
0
Baylor, Dallas
15
0
Emory University, Atlanta
71
2
St. Luke’s Roosevelt, New York
15
0
Sentara, Norfolk
55
0
Texas Cardiac, Lubbock
12
0
St. Joseph Mercy, Ann Arbor
40
1
Cotton-O’Neil, Topeka
12
0
Duke University, Durham
39
0
Ohio State University, Columbus
11
1
University of Arizona, Tucson
38
0
Cleveland Clinic Fnd, Cleveland
9
0
UT Southwestern, Dallas
33
1
London Health Sciences, Ontario
9
0
University of Florida, Gainesville
32
1
Cardiac Surg. Assoc, Kissimmee
8
0
Florida Hospital, Orlando
27
0
Texas Heart Institute, Houston
7
0
Oklahoma VA, Oklahoma City
27
1
Johns Hopkins Univ., Baltimore
7
1
UBC, Vancouver
23
0
Washington University, St. Louis
6
0
Providence Heart, Portland, OR
21
0
Univ Catanzaro, Catanzaro, IT
6
0
WakeMed, Raleigh
20
0
University of Oklahoma, OK City
5
0
Loma Linda Univ., Loma Linda
20
1
Civil Hospital, Sassari, IT
3
1
New Mexico Heart, Albuquerque
19
1
Aurora Health Care , Milwaukee
1
0
University of Alberta, Edmonton
17
2
Univ. Pittsburgh, PA
1
1
The Surgical anatomy of the aortic root. Clinical implications
.
PROTOTYPES
Relationship of TE to Bleed
Horstkotte 1994
Files on USB from Jack Bokros • Art.qt (History, design, outcomes) qt.mov • FDA Data Comparisons, Burnett qt.mov • History, Design, Outcomes.ppt • New Sewing Cuff bmp.ppt • Pre FDA IDE Studies qt.mov • PROACT ACC Emory 3 16 2011 JP cb jb.ppt • Reference Index (references referred to in the presentation) • Rom/lat2012a (broad overview, 15 minutes) qt.mov • Ruyra sewing cuff presentation.ppt • Williams So African 10 year data.ppt • Zilla’s critique of bioprostheses qt.mov “qt.mov” means it is a Quicktime movie. If the file does not open, go to Google, search for Quicktime and download the free application.
PHYSIO-ON X sewing ring :
GOALS
-Favor implantation -Avoid forceful implantation -Avoid undersizing -Avoid Tissue damage -Avoid paravalvular leak -Favor double valve replacement (M-Ao)
Files on USB from Jack Bokros • Art.qt (History, design, outcomes) qt.mov • FDA Data Comparisons, Burnett qt.mov • History, Design, Outcomes.ppt • New Sewing Cuff bmp.ppt • Pre FDA IDE Studies qt.mov • PROACT ACC Emory 3 16 2011 JP cb jb.ppt • Reference Index (references referred to in the presentation) • Rom/lat2012a (broad overview, 15 minutes) qt.mov • Ruyra sewing cuff presentation.ppt • Williams So African 10 year data.ppt • Zilla’s critique of bioprostheses qt.mov “qt.mov” means it is a Quicktime movie. If the file does not open, go to Google, search for Quicktime and download the free application.
Enrollment by Group
As of 1/1/2012
AVR High Risk Group Postrandomization Events Event
Major Bleed Minor Bleed Total Bleed
Control (ptyr=448.4) (2.0 – 3.0) N Rate (%/ptyr) 19 4.24 22 4.91 41 9.14
Test (ptyr=405.0) (1.5 – 2.0) N Rate (%/ptyr) 8 1.97 10 2.47 18 4.44
Rate Ratio
95% CI
P-value
2.15 1.99 2.06
0.90-5.66 0.09-4.70 1.16-3.80
0.064 0.066 0.009
(control/test)
Stroke TIA Neurologic Event
3 3 6
0.67 0.67 1.51
5 7 12
1.23 1.73 2.96
0.54 0.39 0.45
0.08-2.79 0.06-1.70 0.14-1.30
0.394 0.153 0.103
Peripheral TE Thrombosis
1 0
0.22 0.00
3 2
0.74 0.49
0.30 NA
0.01-3.75 NA
0.270 0.137
Major Event (Major bleed, stroke, thrombosis) All Above Events
22
4.91
15
3.70
1.32
0.66-2.75
0.400
48
10.70
35
8.64
1.24
0.78-1.97
0.335
Sudden Death Valve-related death
1 1
0.22 0.22
2 2
0.49 0.49
0.45 0.45
0.01-8.67 0.01-8.67
0.505 0.505
Total Mortality
7
1.56
10
2.47
0.63
0.20-1.84
0.348
Summary • AVR High Risk – Showing some differences at average follow-up of 2.3 years • Total bleeding now significantly less in high risk test group
– Non-inferiority appears to be valid hypothesis – Close out and application to occur in 2012
• Sample inadequate in low risk AVR and MVR – Enrollment should close by in 2012 – Low risk AVR now has patients with over 5 years exposure without events; event rates very low both control and test – MVR trending toward better overall in test group
Actual Computational Fluid Dynamic
Velocity vectors downstream of the ATS valve This long region of stagnation and recirculation persists throughout the systolic phase of the cycle.1 When the valve is closed, the pivot is not purgeable. And this is one of the main reasons that the “open pivot� design was initially rejected by Carbomedics before it was later licensed to ATS. [comments by Jack Bokros] 1. Kelly, SGD. Computational fluid dynamics insights in the design of mechanical heart valves. Artificial Organs 2002;26(7):608-13
Area behind the ATS “abutment” is not purgeable.
Positions of reversed flow within the valve housing ring at three different times up to peak systole.
This “cavity” behind the abutment is not purgeable when the valve is closed.
Mean Gradient Aortic (Late) –US FDA Summary of Safety and Effectiveness SIZE
ATS Standard Valve
On-X
19 mm
20.2 +/- 2.8
9.0 +/- 3.2
21 mm
18.0 +/- 1.6
8.1 +/- 3.2
(18mm AP)
23 mm
13.1 +/- 0.8
6.6 +/- 3.1
(20 mm AP)
25 mm
11.1 +/- 0.8
4.2 +/- 2.5
(22 mm AP)
27/29 mm
8.0 +/- 0.8 (25mm AP)
5.5 +/- 3.0
Enhanced left ventricular mass regression after aortic valve replacement in patients with aortic stenosis is associated with improved Ayyaz Ali, Amit Patel, Ziad Ali, Yasir Abu-Omar, Amber Saeed, Thanos Athanasiou and long-term survival John Pepper
J Thorac Cardiovasc Surg 2011; 142:285-291 DOI: 10.1016/j.jtcvs.2010.08.084