`Ultrasound Navigation through the Heart
`for off-pump Aortic Valved Stent
`Implantation
`Ch Huber, M Nasratulla, M Augstburger, LK von Segesser
`
`Dep. Cardiovascular Surgery
`University Hospital Lausanne,
`CHUV, Switzerland
`
`Currently at: Div. Cardic Surgery
`Brigham and Women’s Hospital
`Boston, MA, USA
`
`Huberch@dr.com
`
`ENDOHEART AG, EX. 2015 Page 1
`EDWARDS LIFESCIENCES CORPORATION (PETITIONER) v. ENDOHEART AG (PATENT OWNER)
`Case No.: IPR2016-00300, U.S Patent No. 8,182,530
`
`
`
`New Valved Stent Design
`Evaluation of a new self-
`expanding Valved Stent
`
`Nitinol Stent
`
`Equine pericard
`(3F Therapeutics)
`
`ENDOHEART AG, EX. 2015 Page 2
`EDWARDS LIFESCIENCES CORPORATION (PETITIONER) v. ENDOHEART AG (PATENT OWNER)
`Case No.: IPR2016-00300, U.S Patent No. 8,182,530
`
`
`
`Self-Expanding Valved Stent
`
`Valved Stent dimensions
`
`Top view
`
`Side view
`
`Bottom
`view
`
`Side view
`
`ENDOHEART AG, EX. 2015 Page 3
`EDWARDS LIFESCIENCES CORPORATION (PETITIONER) v. ENDOHEART AG (PATENT OWNER)
`Case No.: IPR2016-00300, U.S Patent No. 8,182,530
`
`
`
`Delivery device
`
`Patrially loaded
`onto the delivery
`device,
`max diam 9.2 mm
`
`Direction of insertion
`
`Fully crimpt
`
`ENDOHEART AG, EX. 2015 Page 4
`EDWARDS LIFESCIENCES CORPORATION (PETITIONER) v. ENDOHEART AG (PATENT OWNER)
`Case No.: IPR2016-00300, U.S Patent No. 8,182,530
`
`
`
`Ultrasound Navigation
`
`AcuNav
`
`IVUS
`
`ENDOHEART AG, EX. 2015 Page 5
`EDWARDS LIFESCIENCES CORPORATION (PETITIONER) v. ENDOHEART AG (PATENT OWNER)
`Case No.: IPR2016-00300, U.S Patent No. 8,182,530
`
`
`
`Ultrasound Navigation
`
`1.
`
`AcuNav into right atrium
`
`ENDOHEART AG, EX. 2015 Page 6
`EDWARDS LIFESCIENCES CORPORATION (PETITIONER) v. ENDOHEART AG (PATENT OWNER)
`Case No.: IPR2016-00300, U.S Patent No. 8,182,530
`
`
`
`Ultrasound Navigation - AcuNav
`
`ENDOHEART AG, EX. 2015 Page 7
`EDWARDS LIFESCIENCES CORPORATION (PETITIONER) v. ENDOHEART AG (PATENT OWNER)
`Case No.: IPR2016-00300, U.S Patent No. 8,182,530
`
`
`
`Ultrasound Navigation - IVUS
`2.
`
`IVUS inserted into LV apex
`
`ENDOHEART AG, EX. 2015 Page 8
`EDWARDS LIFESCIENCES CORPORATION (PETITIONER) v. ENDOHEART AG (PATENT OWNER)
`Case No.: IPR2016-00300, U.S Patent No. 8,182,530
`
`
`
`Ultrasound Navigation - IVUS
`
`ENDOHEART AG, EX. 2015 Page 9
`EDWARDS LIFESCIENCES CORPORATION (PETITIONER) v. ENDOHEART AG (PATENT OWNER)
`Case No.: IPR2016-00300, U.S Patent No. 8,182,530
`
`
`
`AcuNav typical views of a native aorta
`
`ENDOHEART AG, EX. 2015 Page 10
`EDWARDS LIFESCIENCES CORPORATION (PETITIONER) v. ENDOHEART AG (PATENT OWNER)
`Case No.: IPR2016-00300, U.S Patent No. 8,182,530
`
`
`
`AcuNav typical views of a native aorta
`
`ENDOHEART AG, EX. 2015 Page 11
`EDWARDS LIFESCIENCES CORPORATION (PETITIONER) v. ENDOHEART AG (PATENT OWNER)
`Case No.: IPR2016-00300, U.S Patent No. 8,182,530
`
`
`
`AcuNav typical views of a native aorta
`
`ENDOHEART AG, EX. 2015 Page 12
`EDWARDS LIFESCIENCES CORPORATION (PETITIONER) v. ENDOHEART AG (PATENT OWNER)
`Case No.: IPR2016-00300, U.S Patent No. 8,182,530
`
`
`
`OR setup for off-pump Aortic
`Valved Stent Implantation
`
`Head
`
`Fluoroscopy
`
`AcuNav
`
`IVUS
`
`ENDOHEART AG, EX. 2015 Page 13
`EDWARDS LIFESCIENCES CORPORATION (PETITIONER) v. ENDOHEART AG (PATENT OWNER)
`Case No.: IPR2016-00300, U.S Patent No. 8,182,530
`
`
`
`Left sided thoracotomy
`
`Head
`
`11cm
`incision
`
`LV
`apex
`
`Access through a left sided thoracotomy
`for exposure of the left ventricular apex.
`
`ENDOHEART AG, EX. 2015 Page 14
`EDWARDS LIFESCIENCES CORPORATION (PETITIONER) v. ENDOHEART AG (PATENT OWNER)
`Case No.: IPR2016-00300, U.S Patent No. 8,182,530
`
`
`
`IVUS insertion through the left
`ventricular apex
`
`ENDOHEART AG, EX. 2015 Page 15
`EDWARDS LIFESCIENCES CORPORATION (PETITIONER) v. ENDOHEART AG (PATENT OWNER)
`Case No.: IPR2016-00300, U.S Patent No. 8,182,530
`
`
`
`IVUS finding of a native valve
`
`ENDOHEART AG, EX. 2015 Page 16
`EDWARDS LIFESCIENCES CORPORATION (PETITIONER) v. ENDOHEART AG (PATENT OWNER)
`Case No.: IPR2016-00300, U.S Patent No. 8,182,530
`
`
`
`Off-pump Aortic Valved Stent
`Implantation - A experimental study
`
`Off-pump implantation of a self-expanding
`Valved Stent in the orthotopic aorta over the
`native leaflets.
`
` 5
`
` pigs
`Mean body weight 56±±5kg
`
`Antegrade approach via left thoracotomy and the
`left ventricular apex.
`
`ENDOHEART AG, EX. 2015 Page 17
`EDWARDS LIFESCIENCES CORPORATION (PETITIONER) v. ENDOHEART AG (PATENT OWNER)
`Case No.: IPR2016-00300, U.S Patent No. 8,182,530
`
`
`
`Off-pump Aortic Valved Stent
`Implantation - native aortic measures
`
`Native in-vivo AcuNav
`and IVUS measures:
`
`
` •
`
` Aortic valve diameter: 21.8±0.9mm
` 3.75±0.8cm2
`• Aortic valve area:
`
`• No significant differences were found between both
`techniques
`
`ENDOHEART AG, EX. 2015 Page 18
`EDWARDS LIFESCIENCES CORPORATION (PETITIONER) v. ENDOHEART AG (PATENT OWNER)
`Case No.: IPR2016-00300, U.S Patent No. 8,182,530
`
`
`
`Off-pump Aortic Valved Stent
`Implantation – delivery device insertion
`
`Through the
`LV apex
`
`ENDOHEART AG, EX. 2015 Page 19
`EDWARDS LIFESCIENCES CORPORATION (PETITIONER) v. ENDOHEART AG (PATENT OWNER)
`Case No.: IPR2016-00300, U.S Patent No. 8,182,530
`
`
`
`Off-pump Aortic Valved Stent
`Implantation - IVUS and AcuNav findings
`
`ENDOHEART AG, EX. 2015 Page 20
`EDWARDS LIFESCIENCES CORPORATION (PETITIONER) v. ENDOHEART AG (PATENT OWNER)
`Case No.: IPR2016-00300, U.S Patent No. 8,182,530
`
`
`
`Off-pump Aortic Valved Stent
`Implantation - Results I
`
`AcuNav and IVUS identified:
`
` •
`
` •
`
` Of 5 implanted Valved Stents: 2 were delivered at target
`site
`• One Valved Stent was placed supra-annular
`
`And
`
` Two Valved Stent dislocated into the left ventricle
`because of size-mismatch
`
`ENDOHEART AG, EX. 2015 Page 21
`EDWARDS LIFESCIENCES CORPORATION (PETITIONER) v. ENDOHEART AG (PATENT OWNER)
`Case No.: IPR2016-00300, U.S Patent No. 8,182,530
`
`
`
`Off-pump Aortic Valved Stent
`Implantation - Results II
`
`Intra-Vascular Ultrasound (IVUS) showed:
` Good leaflet motion
`• Full valvular opening and closing in 3 of 3 Valved Stents
`• Planimetric valve orifice was 1.8 ± 0.4cm2
`
` •
`
`
`
`Intra-Cardiac Ultrasound (AcuNav) showed:
`
` •
`
` Low transvalvular gradient
`• No signs of coronary flow impairment
`• A moderate paravalvular leak in 1 of 3 Valved Stents
`
`ENDOHEART AG, EX. 2015 Page 22
`EDWARDS LIFESCIENCES CORPORATION (PETITIONER) v. ENDOHEART AG (PATENT OWNER)
`Case No.: IPR2016-00300, U.S Patent No. 8,182,530
`
`
`
`Off-pump Aortic Valved Stent
`Implantation - IVUS and AcuNav findings
`
`ENDOHEART AG, EX. 2015 Page 23
`EDWARDS LIFESCIENCES CORPORATION (PETITIONER) v. ENDOHEART AG (PATENT OWNER)
`Case No.: IPR2016-00300, U.S Patent No. 8,182,530
`
`
`
`Off-pump Aortic Valved Stent
`Implantation - IVUS and AcuNav findings
`
`ENDOHEART AG, EX. 2015 Page 24
`EDWARDS LIFESCIENCES CORPORATION (PETITIONER) v. ENDOHEART AG (PATENT OWNER)
`Case No.: IPR2016-00300, U.S Patent No. 8,182,530
`
`
`
`Off-pump Aortic Valved Stent
`Implantation - IVUS and AcuNav findings
`
`ENDOHEART AG, EX. 2015 Page 25
`EDWARDS LIFESCIENCES CORPORATION (PETITIONER) v. ENDOHEART AG (PATENT OWNER)
`Case No.: IPR2016-00300, U.S Patent No. 8,182,530
`
`
`
`Off-pump Aortic Valved Stent
`Implantation - Results III
`
`M-Mode of native LAD flow by
`AcuNav prior to Valved Stent
`implantation.
`
`Unchanged flow pattern after
`Valved Stent implantation.
`
`ENDOHEART AG, EX. 2015 Page 26
`EDWARDS LIFESCIENCES CORPORATION (PETITIONER) v. ENDOHEART AG (PATENT OWNER)
`Case No.: IPR2016-00300, U.S Patent No. 8,182,530
`
`
`
`Off-pump Aortic Valved Stent
`Implantation - Complications
`
`Valved Stent dislocation into the left
`ventricle because of size mismatch
`
`ENDOHEART AG, EX. 2015 Page 27
`EDWARDS LIFESCIENCES CORPORATION (PETITIONER) v. ENDOHEART AG (PATENT OWNER)
`Case No.: IPR2016-00300, U.S Patent No. 8,182,530
`
`
`
`Off-pump Aortic Valved Stent
`Implantation - Conclusions I
`
` Simultaneous intravascular and intracardiac
`ultrasound guided off-pump aortic Valved Stent
`implantation via the left ventricular apex and left
`sided thoracotomy is feasible.
`
`
`
`ENDOHEART AG, EX. 2015 Page 28
`EDWARDS LIFESCIENCES CORPORATION (PETITIONER) v. ENDOHEART AG (PATENT OWNER)
`Case No.: IPR2016-00300, U.S Patent No. 8,182,530
`
`
`
`Off-pump Aortic Valved Stent
`Implantation - Conclusions II
`
`IVUS and AcuNav imaging allows for:
`
` •
`
` Adequate aortic dimension assessment
`• Target site identification
`• Valved Stent delivery monitoring
`• Post implantation coronary flow evaluation.
`
`ENDOHEART AG, EX. 2015 Page 29
`EDWARDS LIFESCIENCES CORPORATION (PETITIONER) v. ENDOHEART AG (PATENT OWNER)
`Case No.: IPR2016-00300, U.S Patent No. 8,182,530
`
`
`
`New TOOLS for New GOALS
`Ultrasound Navigation through the Heart
`for off-pump Aortic Valved Stent
`Implantation
`Ch Huber, M Nasratulla, M Augstburger, LK von Segesser
`
`Thank you
`
`Dep. Cardiovascular Surgery
`University Hospital Lausanne,
`CHUV, Switzerland
`
`Currently at: Div. Cardic Surgery
`Brigham and Women’s Hospital
`Boston, MA, USA
`
`Huberch@dr.com
`
`ENDOHEART AG, EX. 2015 Page 30
`EDWARDS LIFESCIENCES CORPORATION (PETITIONER) v. ENDOHEART AG (PATENT OWNER)
`Case No.: IPR2016-00300, U.S Patent No. 8,182,530
`
`
`
`Residual-Coronary \ Sinus-Stent-Index
`RCSSI
`
`A
`
`B
`
`ENDOHEART AG, EX. 2015 Page 31
`EDWARDS LIFESCIENCES CORPORATION (PETITIONER) v. ENDOHEART AG (PATENT OWNER)
`Case No.: IPR2016-00300, U.S Patent No. 8,182,530
`
`
`
`Residual-Coronary \ Sinus-Stent-Index
`RCSSI
`
`VS
`
`Main LCA
`
`A
`
`B
`
`RCSSI = A/B
`RCSSI ≥ 1 no flow impairment
`RCSSI < 1 posibel flow impairment
`
`ENDOHEART AG, EX. 2015 Page 32
`EDWARDS LIFESCIENCES CORPORATION (PETITIONER) v. ENDOHEART AG (PATENT OWNER)
`Case No.: IPR2016-00300, U.S Patent No. 8,182,530
`
`
`
`ENDOHEART AG, EX. 2015 Page 33
`EDWARDS LIFESCIENCES CORPORATION (PETITIONER) v. ENDOHEART AG (PATENT OWNER)
`Case No.: IPR2016-00300, U.S Patent No. 8,182,530
`
`
`
`ENDOHEART AG, EX. 2015 Page 34
`EDWARDS LIFESCIENCES CORPORATION (PETITIONER) v. ENDOHEART AG (PATENT OWNER)
`Case No.: IPR2016-00300, U.S Patent No. 8,182,530
`
`
`
`In Vitro Testing of the Valved Stent
`
`Dynamic tests of the new Valved Stent
`under pulsatile Mock Loop conditions
`
`Tip of IVUS
`probe
`
`ENDOHEART AG, EX. 2015 Page 35
`EDWARDS LIFESCIENCES CORPORATION (PETITIONER) v. ENDOHEART AG (PATENT OWNER)
`Case No.: IPR2016-00300, U.S Patent No. 8,182,530
`
`
`
`Valved Stent in Native Aortic Position -
`Experimental Study
`
`Implantation of the self-
`expanding Valved Stent
`in anatomic aortic position
`
` 6
`
` calves
`Mean body weight 75±2.5 kg
`
`Retrograde aproach via sternotomy and ascending
`aorta. On-pump implantation in 4 animals and off-
`pump implantation after induced ventricular fibrillation
`in 2 animals.
`
`ENDOHEART AG, EX. 2015 Page 36
`EDWARDS LIFESCIENCES CORPORATION (PETITIONER) v. ENDOHEART AG (PATENT OWNER)
`Case No.: IPR2016-00300, U.S Patent No. 8,182,530
`
`
`
`Valved Stent in Native Aortic Position –
`Results I
`
`Intra-Vascular Ultrasound (IVUS) showed:
` Good leaflet motion
`• Full valvular opening and closing in 5 of 6 valves
`• Planimetric valve orifice 1.75±±0.4 cm2
`Intra-Cardiac Ultrasound (AcuNav) showed:
`
` •
`
` •
`
` Low transvalvular gradient
`• No signs of coronary flow impairment
`• Residual-Coronary \ Sinus-Stent-Index (RCSSI) of 1.8±1.2
`
`
`
`ENDOHEART AG, EX. 2015 Page 37
`EDWARDS LIFESCIENCES CORPORATION (PETITIONER) v. ENDOHEART AG (PATENT OWNER)
`Case No.: IPR2016-00300, U.S Patent No. 8,182,530
`
`
`
`Valved Stent in Native Aortic Position –
`Results II
`
`Peak to peak pressure gradient across the
`Valved Stent with aortic blood flow of:
`
`4.5 ± 0.9 L/min
`
`5.3 ± 3.9 mmHg (range 1 to 15 mmHg)
`at invasive measurements
`
`4.7 ± 2.5 mmHg (range 2 to 6 mmHg)
`at Doppler echocardiography
`
`ENDOHEART AG, EX. 2015 Page 38
`EDWARDS LIFESCIENCES CORPORATION (PETITIONER) v. ENDOHEART AG (PATENT OWNER)
`Case No.: IPR2016-00300, U.S Patent No. 8,182,530
`
`
`
`Intra Vascular Ultra Sound (IVUS) and
`AcuNav of the Valved Stent in Native
`Aortic Position
`
`Left Ventricular Outflow tract by
`AcuNav Imaging after Valved
`Stent Implantation
`Note Coronary flow Doppler
`signal during diastol
`
`IVUS Imaging inside a Valved
`Stent in orthotopic aortic
`position
`
`ENDOHEART AG, EX. 2015 Page 39
`EDWARDS LIFESCIENCES CORPORATION (PETITIONER) v. ENDOHEART AG (PATENT OWNER)
`Case No.: IPR2016-00300, U.S Patent No. 8,182,530
`
`
`
`Residual-Coronary \ Sinus-Stent-Index
`RCSSI
`
`ENDOHEART AG, EX. 2015 Page 40
`EDWARDS LIFESCIENCES CORPORATION (PETITIONER) v. ENDOHEART AG (PATENT OWNER)
`Case No.: IPR2016-00300, U.S Patent No. 8,182,530
`
`
`
`Residual Coronary Sinus in a Human
`Heart
`
`ENDOHEART AG, EX. 2015 Page 41
`EDWARDS LIFESCIENCES CORPORATION (PETITIONER) v. ENDOHEART AG (PATENT OWNER)
`Case No.: IPR2016-00300, U.S Patent No. 8,182,530
`
`
`
`Residual Coronary Sinus in a Human
`Heart
`
`ENDOHEART AG, EX. 2015 Page 42
`EDWARDS LIFESCIENCES CORPORATION (PETITIONER) v. ENDOHEART AG (PATENT OWNER)
`Case No.: IPR2016-00300, U.S Patent No. 8,182,530
`
`
`
`Valved Stent in orthotopic Aortic
`Position – Results III
`
`Coronary orifice
`
`Post-mortem control
`of the Valved Stent
`
`ENDOHEART AG, EX. 2015 Page 43
`EDWARDS LIFESCIENCES CORPORATION (PETITIONER) v. ENDOHEART AG (PATENT OWNER)
`Case No.: IPR2016-00300, U.S Patent No. 8,182,530
`
`
`
`Valved Stent in orthotopic Aortic
`Position – Results IV
`
`• One of 6 valves showed
`mild to moderate
`regurgitation
`
` •
`
` One of 6 valves
`moderate paravalvular
`leak due to size
`missmatch.
`
`
`ENDOHEART AG, EX. 2015 Page 44
`EDWARDS LIFESCIENCES CORPORATION (PETITIONER) v. ENDOHEART AG (PATENT OWNER)
`Case No.: IPR2016-00300, U.S Patent No. 8,182,530
`
`
`
`Conclusions I
`
`This new self-expanding Valved Stent design
`allows for quick orthotopic aortic valve
`implantation without compromising coronary
`blood flow and excellent immidiate valve
`function.
`
`ENDOHEART AG, EX. 2015 Page 45
`EDWARDS LIFESCIENCES CORPORATION (PETITIONER) v. ENDOHEART AG (PATENT OWNER)
`Case No.: IPR2016-00300, U.S Patent No. 8,182,530
`
`
`
`Conclusions II
`
`No coronary problems occurred with a Residual-
`Coronary \ Sinus-Stent-Index (RCSSI) >1.
`
`RCSSI has the potential to become a usefull tool
`for screening prior aortic Valved Stent
`procedures.
`
`ENDOHEART AG, EX. 2015 Page 46
`EDWARDS LIFESCIENCES CORPORATION (PETITIONER) v. ENDOHEART AG (PATENT OWNER)
`Case No.: IPR2016-00300, U.S Patent No. 8,182,530
`
`
`
`Conclusions III
`
`Intra-vascular Ultrasound (IVUS) combined with
`Intra-cardiac Ultraound (AcuNav) enables for:
`
` •
`
` Target site identification
`• Measurements and RCSSI estimation
`• Wall and leaflets assessment
`• Deployment monitoring
`• No need for angiography
`
`ENDOHEART AG, EX. 2015 Page 47
`EDWARDS LIFESCIENCES CORPORATION (PETITIONER) v. ENDOHEART AG (PATENT OWNER)
`Case No.: IPR2016-00300, U.S Patent No. 8,182,530
`
`
`
`Residual-Coronary \ Sinus-Stent-Index
`RCSSI
`
`ENDOHEART AG, EX. 2015 Page 48
`EDWARDS LIFESCIENCES CORPORATION (PETITIONER) v. ENDOHEART AG (PATENT OWNER)
`Case No.: IPR2016-00300, U.S Patent No. 8,182,530
`
`
`
`Residual Coronary Sinus Stent Index
`RCSSI
`
`VS
`
`Main LCA
`
`A
`
`B
`
`RCSSI = A/B
`RCSSI ≥ 1 no flow impairment
`RCSSI < 1 posibel flow impairment
`
`ENDOHEART AG, EX. 2015 Page 49
`EDWARDS LIFESCIENCES CORPORATION (PETITIONER) v. ENDOHEART AG (PATENT OWNER)
`Case No.: IPR2016-00300, U.S Patent No. 8,182,530
`
`
`
`Ongoing Studies at CHUV
`
`• Surgical antegrade off-pump implantation
`
`• Coronary flow pattern after Valved Stent
`implantation, CFD of various
`configurations
`• Chronic experiments
`
`ENDOHEART AG, EX. 2015 Page 50
`EDWARDS LIFESCIENCES CORPORATION (PETITIONER) v. ENDOHEART AG (PATENT OWNER)
`Case No.: IPR2016-00300, U.S Patent No. 8,182,530
`
`
`
`Valved Stent Potential Interferance
`with Coronary Flow
`
`ENDOHEART AG, EX. 2015 Page 51
`EDWARDS LIFESCIENCES CORPORATION (PETITIONER) v. ENDOHEART AG (PATENT OWNER)
`Case No.: IPR2016-00300, U.S Patent No. 8,182,530
`
`
`
`Rseidual Coronary Sinus
`
`ENDOHEART AG, EX. 2015 Page 52
`EDWARDS LIFESCIENCES CORPORATION (PETITIONER) v. ENDOHEART AG (PATENT OWNER)
`Case No.: IPR2016-00300, U.S Patent No. 8,182,530
`
`
`
`Valved Stent Flexibility
`
`In-Vitro Evaluation of a new self-expanding
`Valved Stent (3F Therapeutics, CA, USA)
`
`Expanded
`
`Collapsed
`
`ENDOHEART AG, EX. 2015 Page 53
`EDWARDS LIFESCIENCES CORPORATION (PETITIONER) v. ENDOHEART AG (PATENT OWNER)
`Case No.: IPR2016-00300, U.S Patent No. 8,182,530
`
`
`
`Self-Expanding Valved Stent
`
`Nitinol stent
`
`Pericardial
`leaflets
`
`Valved Stent
`
`ENDOHEART AG, EX. 2015 Page 54
`EDWARDS LIFESCIENCES CORPORATION (PETITIONER) v. ENDOHEART AG (PATENT OWNER)
`Case No.: IPR2016-00300, U.S Patent No. 8,182,530
`
`
`
`Ongoing Studies at CHUV
`
`In-Vitro IVUS Imaging of the new Valved Stent
`in the pulsatile Mock Loop.
`Closed
`
`Open
`
`7.4 mm²
`
`120.9 mm²
`
`ENDOHEART AG, EX. 2015 Page 55
`EDWARDS LIFESCIENCES CORPORATION (PETITIONER) v. ENDOHEART AG (PATENT OWNER)
`Case No.: IPR2016-00300, U.S Patent No. 8,182,530