James S. Gammie, MD Professor and Chief, Division of ...€¦ · James S. Gammie, MD Professor and Chief, Division of Cardiac Surgery Chief Medical Officer, Harpoon Medical The Houston

James S. Gammie, MDJames S. Gammie, MD

Professor and Chief, Division of Cardiac Surgery

Chief Medical Officer, Harpoon Medical

The Houston Aortic Symposium

February 23-25, 2017

Disclosure Statement of Financial InterestDisclosure Statement of Financial Interest

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

Affiliation/Financial Relationship Company

• Consulting Fees/Honoraria • Edwards Lifesciences• Correx

• Ownership/Founder • Harpoon Medical

Surgery for Mitral Regurgitation:Who Are We Operating on Today?Who Are We Operating on Today?

DegenerativeDiseaseDisease

N = 13,154 Society of Thoracic Surgeons Adult CardiacN = 13,154 Society of Thoracic Surgeons Adult CardiacDatabase; 2011

FOR DEGENERATIVE MR:

REPAIR BEATS REPLACEMENT EVERY TIMEREPAIR BEATS REPLACEMENT EVERY TIME

REPAIR

Advantages of Repair Compared to Replacement

Lower operative mortality Lower operative mortality Improved left ventricular function Lower risk of stroke Lower risk of infection Lower risk of infection Freedom from anticoagulation and reoperation Superior long-term survival

Mitral Valve Repair or ReplacementMitral Valve Repair or Replacement

“A Patient with a Mitral Prosthesis…“A Patient with a Mitral Prosthesis…

Is a Patient for Life”Is a Patient for Life”

Robert W.M. Frater, MDRobert W.M. Frater, MD

Advantages of Mitral Valve RepairCompared to ReplacementCompared to Replacement

2000 – 2007

N = 58,370 Mitral Operations

Trends in Mitral Valve Surgery in the United States: Resultsfrom the Society of Thoracic Surgeons Adult Cardiac

Ann Thorac Surg 2009;87:1431-1439

from the Society of Thoracic Surgeons Adult CardiacDatabase

Ann Thorac Surg 2009;87:1431-1439

Procedure N # ofdeaths

ObservedMortality

Odds ratio (95% CI) (MVrepair vs MV

Riskstandardizeddeaths Mortality repair vs MV

replacement)standardizedmortality %

(95 % CI)**

MV 30811 414 1.34 Unadjusted Adjusted 1.65MV

Repair

30811 414 1.34 Unadjusted Adjusted 1.65

(1.49, 1.80)0.34

(.30, .39)

0.52(.45,.59)

MV 17007 651 3.83 (reference) (reference) 2.96

Replace (2.72, 3.20)

* Adjusted for 25 risk factors plus year of surgery; p < 0.0001 repair compared toreplacement

** Directly adjusted across 10 propensity groups; p < 0.001

REPAIR REPLACE

STROKE / YR 1.15 +/- 0.1 % 2.2 +/- 0.4 %STROKE / YR 1.15 +/- 0.1 % 2.2 +/- 0.4 %

INFECTION (PVE) / YR 0.1 % 1 %

Russo A, J. Am. Coll. Cardiol. 2008;51;1203-1211Wang A, JAMA. 2007;297:1354-1361Wang A, JAMA. 2007;297:1354-1361

REPAIR REPLACE




REPAIR REPLACE




Advantages of Mitral Valve Repair

Mitral Valve Disease Segmentation

Primary (Degenerative) Functional

Percent of Total MR population*: 50 % 50%

Indications for Intervention: Well Established Not Clear (IIB) –Indications for Intervention: Well Established Not Clear (IIB) –COAPT?

Operative Therapy: Repair Replacement

Good Operative Therapy? YES NO

Is Therapy Applied Consistently? NO (replacement) NO

Patients with Severe MR USA*: 800,000 800,000

Annual Mitral Valve Surgery Rate: 5% 0.75 %Annual Mitral Valve Surgery Rate: 5% 0.75 %

*Canaccord Genuity 2016

Future of Catheter-Based Mitral Intervention

Near Future:

TMVR: BIG HURDLES: Access, Thrombosis,Paravalvular leak, LVOT obstruction, etc.BIG Investment – BIG EngineeringBIG Investment – BIG EngineeringWhen it works… IT IS STILL A MITRAL REPLACEMENT!

Repair for Degenerative Disease:Mitraclip: suboptimal (lessons from surgery)Goal:

Replicate ePTFE Non-Resectional MV Repair

*Canaccord Genuity 2016

Replicate ePTFE Non-Resectional MV Repair

Transapical, Beating-Heart*Canaccord Genuity 2016

Evolution of Repair for Degenerative Disease

Evolution of Repair for Degenerative DiseaseUniversity of Maryland ExperienceUniversity of Maryland Experience

100Leaflet resection Neochordal Insertion

80

40

60

20

40

0

20

2004 2005 2006 2007 2008 2009 2010 2011 2012

Year

2004 2005 2006 2007 2008 2009 2010 2011 2012

Mitralvalverepair.org

Vol 6, Supplement 1 (March 2014): Journal of Thoracic Disease



Vol 6, Supplement 1 (March 2014): Journal of Thoracic Disease


Courtesy A. M. Gillinov, MD

CONFIDENTIAL Slide 23 2/23/2017

http://www.visibleheart.com

Image-Guided Trans-Apical Mitral Valve Repair:A Better WayA Better Way

J.S. Gammie

COMPREHENSIVE HEART CENTER

J.S. Gammie

Harpoon: Fast Simple Procedure

Real-Time Titration of ePTFE Cordal Length

Harpoon Mitral Valve Repair System

Beating-Heart Surgical Repair

in DMR PatientsInitial Focus:Posterior Prolapse

Applicable Pts:

Harpoon Mitral Valve Repair System

in DMR Patients Posterior ProlapseApplicable Pts:>60% of DMR today

Small 3mm shaft profile houses 21 gauge

Strong proprietary anchor, place cords

needle with pre-wound ePTFE suture

Key Benefits

Strong proprietary anchor, place cords

anywhere, no need to “catch” the leaflet

Dedicated 9 Fr hemostatic introducer

Improved SafetyProfile

Surgical-LikeOutcomes

SimplifiedRepair

Dedicated 9 Fr hemostatic introducer

minimizes trauma & blood loss

Harpoon Technology:

Anchoring EQUIVALENT to surgical ePTFE:Anchoring EQUIVALENT to surgical ePTFE:

Conventional Harpoon

Pull-out Force (N) 8.34 ± 3.29 8.58 ± 3.34Pull-out Force (N) 8.34 ± 3.29 8.58 ± 3.34N = 11 Hearts; P=0.93

*Normal Chordal Force = 0.1 - 0.3 N*Normal Chordal Force = 0.1 - 0.3 N

Harpoon Transapical RepairPatient # 1Patient # 1

Intraprocedural TEE (Knot deployment)

Intraprocedural TEE (ePTFE artificial cords tightened)

Intraprocedural TEE (ePTFE artificial cords tightened)

6 MONTH TTE

MR Grade: NONE/TRACE

ONE YEAR TTE


TWO YEAR TTE


Clinical Results: Early Feasibility Study

Two Study Centers:• Jagellonian University John Paul II Hospital,

KrakowKrakow• Institute of Cardiology, Warsaw

Enrollment Complete:Enrollment Complete:• 13 patients enrolled with follow-up ongoing• February 2015 – February 2016• February 2015 – February 2016

Echocardiography Core Lab:• Massachusetts General Hospital (J. Hung, MD)• ASE Grading of MR• ASE Grading of MR

• None/Trace• Mild• Moderate• Moderate• Severe

Study Objective: Evaluate Safety and Performance of the HarpoonDevice

Primary Endpoints:• Harpoon Device Performs as Designed, Successfully Implant 1 or more

ePTFE CordsePTFE Cords• Demonstrate MR Reduction from Severe to </= Moderate MR• Measure of adverse events in accordance with MVARC

Inclusion Criteria:Inclusion Criteria:• Severe Degenerative Mitral Regurgitation• Isolated Posterior Leaflet Prolapse• Good Predicted Surface of Coaptation• Good Predicted Surface of Coaptation

Exclusion Criteria:• STS PROM Risk > 6• STS PROM Risk > 6• EF < 40 %

PT # Sex AgeSTSRisk

NYHAClass

LVEF

1 F 65 0.76 II 651 F 65 0.76 II 652 M 68 1.09 III 503 M 62 0.60 II 704 M 57 0.69 II 604 M 57 0.69 II 605 M 42 0.22 II 606 M 63 0.46 II 607 M 59 0.34 I 557 M 59 0.34 I 558 M 89 4.57 III 739 M 82 2.50 II 54

10 M 73 1.41 I 6573 1.41 I 6511 M 51 0.21 III 6512 M 80 1.50 III 5713 M 66 0.58 III 79

MEANMEAN 66 1.15 62

PT # Sex AgeSTSRisk

NYHAClass

LVEF

1 F 65 0.76 II 651 F 65 0.76 II 652 M 68 1.09 III 503 M 62 0.60 II 704 M 57 0.69 II 604 M 57 0.69 II 605 M 42 0.22 II 606 M 63 0.46 II 607 M 59 0.34 I 557 M 59 0.34 I 558 M 89 4.57 III 739 M 82 2.50 II 5410 M 73 1.41 I 6573 1.41 I 6511 M 51 0.21 III 6512 M 80 1.50 III 5713 M 66 0.58 III 79

MEANMEAN 66 1.15 62

PT #Days PostProcedure

ePTFE CordsImplanted

IntroducerTime

Skin-to-SkinTime

Residual MR

1 622 4 0:33 1:49 NONE/TRACE1 622 4 0:33 1:49 NONE/TRACE2 620 3 0:21 1:35 NONE/TRACE3 570 3 0:48 1:57 NONE/TRACE4 72 4 0:58 2:47 MILD4 72 4 0:58 2:47 MILD5 520 3 0:27 1:23 NONE/TRACE6 465 4 0:55 2:33 MILD7 464 4 0:25 1:29 NONE/TRACE8 419 3 0:20 1:53 MILD8 419 3 0:20 1:53 MILD9 419 5 0:30 1:14 NONE/TRACE10 231 3 0:49 1:12 NONE/TRACE11 367 4 0:51 2:08 NONE/TRACE11 367 4 0:51 2:08 NONE/TRACE12 271 4 0:41 1:51 NONE/TRACE13 271 4 0:37 2:01 NONE/TRACE

MEAN 3.7 0:38 1:50MEAN 3.7 0:38 1:50

PT #Days PostProcedure

ePTFE CordsImplanted

IntroducerTime

Skin-to-SkinTime

Residual MR

1 622 4 0:33 1:49 NONE/TRACE1 622 4 0:33 1:49 NONE/TRACE2 620 3 0:21 1:35 NONE/TRACE3 570 3 0:48 1:57 NONE/TRACE4 72 4 0:58 2:47 MILD4 72 4 0:58 2:47 MILD5 520 3 0:27 1:23 NONE/TRACE6 465 4 0:55 2:33 MILD7 464 4 0:25 1:29 NONE/TRACE8 419 3 0:20 1:53 MILD8 419 3 0:20 1:53 MILD9 419 5 0:30 1:14 NONE/TRACE10 231 3 0:49 1:12 NONE/TRACE11 367 4 0:51 2:08 NONE/TRACE11 367 4 0:51 2:08 NONE/TRACE12 271 4 0:41 1:51 NONE/TRACE13 271 4 0:37 2:01 NONE/TRACE

MEAN 3.7 0:38 1:50MEAN 3.7 0:38 1:50

• No Mortality• No Mortality

• No Stroke

• No Renal Failure• No Renal Failure

• No Myocardial Infarction

• No Blood Transfusion• No Blood Transfusion

• No Conversion to Open Heart Surgery• No Conversion to Open Heart Surgery

• Two Reoperations for PericardialEffusions (POD 5, 13)

• Two Reoperations for Recurrent MR (POD72, 231)72, 231)

– 1st Patient ePTFE cord untied at apical pledget

– 2nd Patient native anterior chord ruptured– 2 Patient native anterior chord ruptured

– Both patients received successful re-operations, are alive and doing well

Reoperation

Six Months: MR Grade: Severe

Bicommissural view

Red arrows: Harpoon knots

Green Arrow: unsupported lateralGreen Arrow: unsupported lateralaspect of posterior leaflet

ePTFE knots well-incorporated:ePTFE knots well-incorporated:

Suboptimal (basal) targeting Suboptimal (basal) targeting

Excellent endothelialization at 7 months

No leaflet destruction from Harpoon ePTFE cords No leaflet destruction from Harpoon ePTFE cords

Transapical Artificial ePTFE Cordal Repair DoesNOT Preclude Subsequent Conventional RepairNOT Preclude Subsequent Conventional Repair

Mitraclip

Harpoon

Geidel S et al Submitted for Publication

Mitraclip

Preop 30 Day P Value

LVEDD (mm) 54 47 <0.0001

EDV (ml) 139 106 0.007

LVEF (%) 69 63 0.08

LA Dimension(mm) 46 39 0.001

LA Volume (ml) 117 81 0.003

Mitral Annular 40 35.6 0.004Mitral AnnularDimension (mm) 40 35.6 0.004

RVSP (mmHg) 47 32 0.23


LVEDD (mm) 54 47 <0.0001

EDV (ml) 139 106 0.007

LVEF (%) 69 63 0.08


LA Volume (ml) 117 81 0.003


RVSP (mmHg) 47 32 0.23


LVEDD (mm) 54 47 <0.0001

EDV (ml) 139 106 0.007

LVEF (%) 69 63 0.08


LA Volume (ml) 117 81 0.003


RVSP (mmHg) 47 32 0.23

Transapical ePTFE ReplacementTreats SAM !Treats SAM !

SAM NO SAMSAM NO SAM

Patient0

Number ofChords

Screening / Baseline 30 Days 6 Months

1 4 Severe Mild None/Trace1 4 Severe Mild None/Trace

2 3 Severe None/Trace Moderate

3 3 Severe None/Trace None/Trace

4 4 Severe Moderate Converted4 4 Severe Moderate Converted


6 4 Severe Moderate Moderate

7 4 Severe Mild Mild7 4 Severe Mild Mild

8 3 Severe Mild None/Trace

9 5 Severe Mild Mild

10 3 Severe Mild Severe10 3 Severe Mild Severe

11 4 Severe None/Trace Mild



Patient0

Number ofChords















Patient0

Number ofChords















Median Follow-Up 580 Days (386-787)Median Follow-Up 580 Days (386-787)

• 100% Survival

• No Late Stroke• No Late Stroke

• No Thromboembolism

• No Repaired Valve InfectiveEndocarditisEndocarditis

Harpoon: CE trial enrolling; CE Mark est. Q2 2017

US IDE Trials: Randomized vs. SurgeryUS IDE Trials: Randomized vs. Surgery

Ongoing Device Iteration

Patient Selection and Procedural Refinement

CONCLUSIONSINITIAL CLINICAL EXPERIENCEINITIAL CLINICAL EXPERIENCE

BEATING-HEART, IMAGE-GUIDED,TRANSAPICAL MITRAL VALVE REPAIR:TRANSAPICAL MITRAL VALVE REPAIR:

Safe

100 % Procedural Success 100 % Procedural Success

Effective and Durable MR Reduction

Adoptable Adoptable

Does Not Preclude Subsequent Open Mitral ValveRepairRepair

Can Address the Large Majority of Degenerative MitralValve PathologyValve Pathology

Favorable Reverse Remodeling

CONCLUSIONSINITIAL CLINICAL EXPERIENCEINITIAL CLINICAL EXPERIENCE

BEATING-HEART, IMAGE-GUIDED,TRANSAPICAL MITRAL VALVE REPAIR:TRANSAPICAL MITRAL VALVE REPAIR:

Real-time Titration of ePTFE Cords on Beating Real-time Titration of ePTFE Cords on BeatingHeart

Provides tactile / haptic feedback to operator Provides tactile / haptic feedback to operator

Maximize Coaptation

Only Implant = ePTFE Suture

NO: sternotomy, cross clamp, cardioplegia, or NO: sternotomy, cross clamp, cardioplegia, orbypass

Patients Treated with TransapicalePTFE Artificial CordsePTFE Artificial Cords

600

400

500

300

400

100

200

0

100

2010 2011 2012 2013 2014 2015 2016

Year

2010 2011 2012 2013 2014 2015 2016

Transapical ePTFE Cordal Mitral Repair Conclusions

Key Advantages:

• Sole Implant = ePTFE Suture• Beating-Heart, Less Invasive• Beating-Heart, Less Invasive• NO: sternotomy, cross clamp, cardioplegia, or

bypass• Outstanding Safety Profile• Outstanding Safety Profile• No Fluoroscopy/Radiation• Provides Haptic Feedback to Operator• Provides Haptic Feedback to Operator• Easy to Learn; “Reference-quality” Repair

Accessible to All

Transapical ePTFE Cordal Mitral Repair Conclusions

Key Advantages:

• Real-time Titration of ePTFE Cordal Lengthon Loaded Heart: Maximize Coaptationand Repair Qualityand Repair Quality

• Encourage Earlier Intervention In MR• SAM is easily treatable• SAM is easily treatable• Favorable Reverse Ventricular Remodeling• Does NOT Preclude Subsequent

Conventional RepairConventional Repair• Effective, Durable MR Reduction

Documents

James S. Gammie, MD Professor and Chief, Division of ...€¦ · James S. Gammie, MD Professor and Chief, Division of Cardiac Surgery Chief Medical Officer, Harpoon Medical The Houston