MOMENTUM and ENDURANCE What Do These Trials Tell Us

About Pump ThrombosisSimon Maltais, MD PhDVice-Chair of Clinical Practice

Director of MCS ProgramDepartment of Cardiovascular Surgery

Mayo Clinic, Rochester, MNAATS MCS 2018, Houston (TX)

Relevant financial relationship(s) with industry: Paid consultant for Medtronic, Abbott, and Clearflow Inc.

I do NOT intend to discuss off-label/investigative uses(s) of commercial product(s)/devices(s) during this presentation

Disclosures

Cut to the Chase

We may NOT have reached the perfect pump; but were are closer

We still need to gather datagood one

Pump is only one dweller in a very complex system

2011 MFMER | 3149555-4

What we have learned from these 2 trials

Not muchbut a bit more

Non-physiologic blood flowin ascending aorta Aortic root dilation AV closure

AV leaflet fusion AV regurgitation

Low-pulsatile or non-pulsatile flow to end-organs

AVM formation GI bleeding Epistaxis

Shear stress of blood Hemolysis Acquired vWd

Risk of infection Driveline infection Pocket infection

Need for anticoagulation System thrombosis Increased risk of

thromboembolism (e.g. stroke, renal infarcts, ischemic bowel, MI)

Continuous Flow Pump Disease

Patient Milieu Sex, age, BMI, prior stroke, ischemic etiology,

AF, hypercoaguabledisorder

Pump Provider

Patient

Pump Provider

Patient

How they are the same.

Similarities do exist with current 2nd and 3rd generation pumps

survival vs. OMM (DT pts) quality of life

Physiological similarities also exist

Decongestion, RV function

PHYSIOLOGIC IMPACT IS VASTLY DIFFERENT!

Wealth of literature to support this Different in MANY different areas

Unloading Hemocompatibility

vWF, hemolysis profiles

Physiologic differences exist, so patient OUTCOMES will be different!

aortic pressure AX: unloading at rest and exercise AX: flow at maximal RPM CFG: power at similar flow AX: risk of suck-down

AX: steeper HQ curves sensitivity to preload and afterload risk of suck-down

CFG: lower power consumption for given flow

One Month Post-LVAD All LVADs HMII HVAD P

Pre-LVAD 73 73 73 0.93

One Month Post-LVAD 8784 153100 4528 0.0002Three Months Post-

LVAD 160340 252473 7589 0.016

Severity of vWF degradation by devices

vWF degradation more severe in patients with HM II

Maltais et al., ISHLT 2016

vWF HMWM Prague Analysis

Netuka et al: JHLT, 2016

Res

idua

l HM

W m

ultim

ers

(%)

HMII HM3

P

vWF HMWM Prague Analysis

Netuka et al: JHLT, 2016

HMWM preserved 50% at 45 daysHMWM preserved

What do we know so far?

Major physiologic differences

Disparate biocompatability

How does this translate into clinical outcomes?

Pump Provider

Patient

Patient #1

45 year old , NYHA IV, IDCMBSA 1.7, BMI 19 kg/m2No PMH, implant as BTTEcho: LV EF 15%, mod RVD, no AR, TR

Cath: CVP 18, PAP 48/18 (28), PCWP 20

Patient #1

45 year old , NYHA IV, IDCMBSA 1.7, BMI 19 kg/m2 No PMH, implant as BTTEcho: LV EF 15%, mod RVD, no AR, TR

Cath: CVP 18, PAP 48/18 (28), PCWP 20

survival: RV failure, inotropes, RVAD, respiratory failure, renal failure

Death from stroke/bleeding: 1.9 Death from sepsis: no cut off 1 yr survival

1.9 83%

Eur J Cardio-Thoracic Surgery 2013;43:1036-42

Patient #2

58 year old , NYHA IV, ICMBTTChronic AF, prior CVA, PVDEcho: LV EF 15%, mod RVD, no AR, TR

Cath: CVP 10, PAP 48/18 (28), PCWP 25

Patient #2

58 year old , NYHA IV, ICMBTTChronic AF, prior CVA, PVDEcho: LV EF 15%, mod RVD, no AR, TR

Cath: CVP 10, PAP 48/18 (28), PCWP 25

ASA < 81 mgPreoperative atrial fibrillation

Months post implant

Cum

ulat

ive

inci

denc

e

Ischemic 539 244 125 61 35 22 12 5 4 1 1Non-ischemic 606 291 147 73 39 17 6 3

P=0.008

Ischemic

Non-ischemic

MCSRN

ISHLT 2016 Oral Presentation, Baltimore, MD

Chart1

1st Qtr1st Qtr1st Qtr

2nd Qtr2nd Qtr2nd Qtr

3rd Qtr3rd Qtr3rd Qtr

4th Qtr4th Qtr4th Qtr

East

West

North

Sheet1

EastWestNorth

1st Qtr

2nd Qtr

3rd Qtr

4th Qtr

To resize chart data range, drag lower right corner of range.

Neurological Events

HR P valueAge (per 10y increase) 6.54 0.09Female vs. Male 0.38 0.54BMI 0.71 0.87INTERMACS 1 vs. others 6.91 0.07Ischemic etiology 4.60 0.03Device type factor (HVAD:HMII)

4.30 0.04

Creatinine 8.00 0.05

MCSRN

Choosing the RIGHT pump

Tailoring pump therapy based on numerous considerations, this will continue to stay true with HMIII

Device therapy could be optimized in various pt populations

Enhance late outcomes

Pump Provider

Patient

Make Mistakes, but DONT repeat them

41/45 pt with INR < 2.021/41 pt with INR < 1.61 TE event1 suspected PT

10/331 thrombotic events 58/331 hemorrhagic events INR < 1.5 40% ICVA INR > 2.5 bleeding

INR 1.5-2.5 appropriate

3 groups of heparin bridging ICVA, HCVA, PT transfusion in heparin group Heparin use predicted bleeding

Mehra, JHLT 2014

PREVENT Recommendations

References:1Adamson RM, Mangi AA, Kormos RL, J Card Surg. 2015 Mar;30(3):296-92Klodell CT, Massey HT, Adamson RM. J Card Surg. 2015 Oct;30(10):775-80

Surgical Recommendations1 Medical Recommendations2

Anticoagulation In patients without persistent bleeding, bridge with heparin; goal PTT of 40-45 sec (48 hours); PTT of 50-60 sec (96 hours).

Initiate warfarin within 48 hours; Target INR: 2.0-2.5.

Antiplatelet Initiate ASA therapy (81-325 mg daily), 2-5 days post HMII implantation.

Pump Speed Maintain > 9000 RPM and Avoid < 8600 RPMs.

Blood Pressure Maintain mean arterial pressure (MAP) < 90 mmHg.

Results - Primary Endpoint Confirmed Pump Thrombosis at 3 Months

P=0.003

2.9 %

8.4%1

References:1Starling, Moazami, Silvestry et al. NEJM 2014 Jan

2;370(1):33-40

Perc

ent o

f Pum

ps

PREVENT NEJM 3 Center Study1

Chart1

PREVENT

NEJM - 3 Center Experience

Series 1

0.029

0.084

Sheet1

Series 1Error

PREVENT2.90%0.027

NEJM - 3 Center Experience8.40%0.055

HVAD Thrombosis

Najjar et. Al. JHLT 2014, 33: 23-34

True Impact of Technology

What we TRULY have learned

Outcomes depend on pump technology..but also provider and patient factors

Subgroup analysis needs to be data driven and we have lo be critical; move past single-center anecdotes

Study of similar pump technology

Conclusions

Story of MCS has been one of progressive improvements

While we are much closer, the data to date shows we can continue to improve

Thinking we have will result in stagnation

Thank you!Maltais.Simon@mayo.edu

2011 MFMER | 3149555-62

MOMENTUM and ENDURANCE What Do These Trials Tell Us About Pump ThrombosisDisclosuresCut to the ChaseSlide Number 4Slide Number 5Slide Number 6Slide Number 7Slide Number 8How they are the same.PHYSIOLOGIC IMPACT IS VASTLY DIFFERENT! Slide Number 11Slide Number 12Slide Number 13Slide Number 14Slide Number 15Slide Number 16Severity of vWF degradation by devicesvWF HMWM Prague AnalysisvWF HMWM Prague AnalysisWhat do we know so far?Slide Number 21Slide Number 22Slide Number 23Slide Number 24Slide Number 25Slide Number 26Slide Number 27Slide Number 28Slide Number 29Patient #1Patient #1Slide Number 32Slide Number 33Patient #2Patient #2Slide Number 36Slide Number 37Slide Number 38Choosing the RIGHT pumpSlide Number 40Slide Number 41Slide Number 42Slide Number 43Slide Number 44Slide Number 45Slide Number 46Slide Number 47Slide Number 48Slide Number 49PREVENT RecommendationsResults - Primary Endpoint Confirmed Pump Thrombosis at 3 MonthsSlide Number 52Slide Number 53Slide Number 54Slide Number 55Slide Number 56Slide Number 57Slide Number 58Slide Number 59What we TRULY have learned ConclusionsThank you!