lvad update for primary care a bit of past, present and future

LVAD Update for Primary Care A bit of past, present and Future

Salman Gohar, MD

Advanced Heart Failure / MCS Service

BSW Health

Disclosures

• I have no disclosures

2

Background

• AHF Problem

• Historical perspective

• Complications

• Referral for Advanced HF therapies

• Current Trends

• Future directions

3

Implications of heart failure in the U.S.1-4

4

References: 1. MozaffarianD, Benjamin EJ, Go AS, et al. Heart disease and stroke statistics—2016 update: A report from the American Heart Association. Circulation. 2016;133(4):e38-e360. 2. Centers for Disease Control and Prevention (CDC) Heart Failure Fact Sheet. https://www.cdc.gov/dhdsp/data_statistics/fact_sheets/fs_heart_failure.htm(accessed August 6, 2018). 3. DunlaySM and Roger VL. Understanding the epidemic of heart failure: past, present, and future. Curr Heart Fail Rep. 2014;11(4):404-415. 4. UNOS (United Network for Organ Sharing). Heart Transplants, 1988-2017. https://optn.transplant.hrsa.gov/data/view-data-reports/national-data/# (Accessed Aug. 6, 2018).

https://www.cdc.gov/dhdsp/data_statistics/fact_sheets/fs_heart_failure.htm

https://optn.transplant.hrsa.gov/data/view-data-reports/national-data/

Heart failure is the leading cause of death after cancer

5

References: 1. Cetin K, Ettinger DS, Hei Y-J, et al. Survival by histological subtype in stage IV nonsmall cell lung cancer based on data from the Surveillance, Epidemiology and End Results Program. Clin Epidemiol. 2011;3:139-148. 2. Wang Y, Schrag D, Brooks GA, et al. National trends in pancreatic cancer outcomes and pattern of care among Medicare beneficiaries, 2000-2010. Cancer. 2014;120(7):1050-1058. 3.Lee DS, Austin PC, Rouleau JL, et al. Predicting mortality among patients hospitalized for heart failure: derivation and validation of a clinical model. JAMA. 2003;290(19):2581-2587.

• Severe exercise intolerance

• Heart failure wasting syndrome

• Cardiorenal syndrome

• Right heart failure

• Inotrope dependence

6

The Late Stage Heart Failure Patient

Defining Advanced Heart Failure

Yancy et al. 2013 ACC/AHA Guideline for the Management of Heart Failure. Circulation June 5, 2013

Clinical Course of Heart Failure

Circulation 2012, 125:1928-1952

Survival after HF Hospitalization

Setoguchi et al. Am Heart J 2007

10

MECHANICAL CIRCULATORY SUPPORTA HISTORICAL PERSPECTIVE

11Charles Lindbergh and Alexis Carrel by Samuel Johnson Woolf. © Estate of S.J. Woolf. Collection of the National Portrait Gallery, NPG.87.TC2

First Heart Lung Machine model

12

John Gibbon – First Heart Lung Machine – 1953

John H. Gibbon, Jr. and the first successful heart-lung machine (images courtesy of the Thomas Jefferson University library, Philadelphia, PA).

Domingo Liotta – The Argentinine

13

April 21, 1966,

Department of Surgery of Baylor College of Medicine in Houston in 1961

the Liotta-DeBakey Paracorporeal Left Ventricular Assist Device (LVAD)

August 6th 1966 – First Success

14

• Esperanza del Valle V• Double valve replacement• Post Cardiotomy shock

with failure to wean from CPB

• Place on VAD for 10 days • Complete recovery

Heartmate XVE : Pulsatile LVAD

16NEJM. 2001. 345(20):1435-1443.

REMATCH 2001

Eligible population

1. New York Heart Association functional class IV for 60 days

2. LVEF <25%

3. Peak oxygen consumption <14 ml/min/kg (unless on balloon pump, intravenous inotropes, or physically unable to perform exercise test) or

4. intra-aortic balloon pump or

5. IV inotrope dependent for 14 days

17

• Heartmate XVE vs. Medical Management

• DT

• N = 129

• Prospective 1:1

NEJM. 2001. 345(20):1435-1443.

REMATCH 2001

18

52%

25%

23%

8%

NEJM. 2001. 345(20):1435-1443.

Pulsatile Generation: Rise of the machines

19

As of November 2019 :– 179 Active Sites– 25,097 Patients Enrolled

20

May 2005

21J Am Coll Cardiol. 2015 Jun 16;65(23):2542-55

Is Pulse necessary? Maybe not…

HM II: Co-axial Flow CF-LVAD

22Rogers J et al NEJM 2017

Pumping Co-Axially

23

Archimedes Screw in Egypt

http://www.waterencyclopedia.com/Po-Re/Pumps-Traditional.html

HEARTMATE II : DT trial 2009

24

Eligible population

1. New York Heart Association functional class IIIB or IV symptoms for >45 of the last 60 days

2. LVEF <25%, and peak oxygen consumption <14 ml/min/kg (unless on balloon pump, intravenous inotropes, or physically unable to perform exercise test) or

3. IABP dependent for 7 days or

4. IV inotrope dependent for 14 days

• Prospective randomized 2:1 HeartMate II vs. HeartMate XVE

• DT

• 1- and 2-yr HeartMate II survival

HM DT Trial 2009

25N Engl J Med 2009; 361:2241-2251

68%

58%

55%

24%

Adverse Effect Profile:

26N Engl J Med 2009; 361:2241-2251

HM II BTT/ DT: Effect on NYHA FC

27JACC Volume 55, Issue 17, 27 April 2010, 1835-1836

28

HM II BTT/ DT: Effect on 6MWD

JACC Vol 55, Issue 17, 27 April 2010, 1835-1836

29

HM II BTT/ DT: Effect on QoL

• Changes in quality of life assessed with the Minnesota Living With Heart Failure(MLWHF) Questionnaire

• Lower values signify improved quality of life.

JACC Vol 55, Issue 17, 27 April 2010, 1835-1836

https://www.sciencedirect.com/topics/nursing-and-health-professions/heart-failure

HVAD : Centrifugal Flow CF-LVAD

30Rogers J et al NEJM 2017

Heartware DT trial - Endurance

31N Engl J Med 2017; 376:451-460

Intention to Treat analysis

Survival at 24 months free of disabling stroke or reoperation toReplace or remove the pump

32

CF-LVAD: Altering Physiology

• P

32

Driveline

Doppler BP

Pulse

VAD “ Hum”

Controller/Alarms

Cardiology Clinics 2007;25:553-64

Critical Role of Echo

• LVAD speed optimization

• Evaluation of pump function

• Evaluation of new symptoms

• Thrombus suspicion

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Understanding Advanced HFNYHA FC III- IV : INTERMACS

INTERMACS‡ Registry = Interagency Registry for Mechanically Assisted Circulatory Support

INTERMACS Profiles

Circulation 2011, 123:1559-1568

Patient Profile/ Status: INTERMACS Levels

1. Critical cardiogenic shock

2. Progressive decline

3. Stable but inotrope dependent

4. Recurrent advanced HF

5. Exertion intolerant

6. Exertion limited

7. Advanced NYHA III

INTERMACS: Patient Selection

Degrees of Class IV

AMBULATORY

HEART FAILURE

PATIENTS

37J Am Coll Cardiol. 2015 Jun 16;65(23):2542-55

INTERMACS : A Guide to Timing for therapy

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MECHANICAL CIRCULATORY SUPPORTCOMPLICATIONS

LVAD : Complications– Hemotocompatibilty

• CVA (Hemorrhagic and Thrombotic)

• Pump thrombus

• GI bleeding

– Device malfunction• Driveline infection

• Sepsis/ Pump infection

• Short to shield

– RV dysfunction

– Arrhythmias

– New de novo AR

42

LVAD: GI Bleeding

• AVM angiogenesis

• 100% loss of HMW vWF factor

43J Thorac Cardiovasc Surg 2009;137: 208-15

HVAD : Stroke

44N Engl J Med 2017;376:452-60

JACC Heart Failure 2015;3:818-28

45

LVAD therapy : Complications

INTERMACS

46

LVAD TherapyCURRENT DEVICES

47

LVAD : Evolution

1998 2008 2017BTT 1998DT 2002

BTT 2008DT 2010

ST (BTT) 2017LT (DT) 2018

Con tinuous flow (axial)

Ov er 26,600 patients implanted with patients on t h erapy out to 5 a nd 10+ years1

Con tinuous flow (centrifugal)w ith Full Ma gLev™ Flow Technology

T h e best published outcomes for

cont inuous-flow LVADs2-6

Pu lsatile flow

First LVAD FDA approved for DT

47

Hea rtMate VE™ LVAD Hea rtMate II™ LVAD Hea rtMate 3™ LVAD

References: 1. Abbott data on file as of May 10, 2018. SJM-HM-1016-0032(3). 2. Mehra MR, Goldstein DJ, Uriel N, et al. Two-Year Outcomes with a Magnetically Levitated Cardiac Pump in Heart Failure. N Engl J Med. 2018;378(15):1386-1395. 3. Rogers JG, Pagani FD, Tatooles AJ, et al. Intrapericardial Left Ventricular Assist Device for Advanced Heart Failure. N Engl J Med. 2017;376:451-60. 4.Starling RC, Estep JD, Horstmanshof DA, et al. Risk Assessment and Comparative Effectiveness of Left Ventricular Assist Device and Medical Management in Ambulatory Heart Failure Patients: The ROADMAP Study 2-Year Results. J Am Coll Cardiol HF. 2017;5:518-527. 5. Jorde UP, Kushwaha SS, Tatooles AJ, et al. Results of the destination therapy post-food and drug administration approval study with a continuous flow left ventricular assist device: a prospective study using the INTERMACS registry (Interagency Registry for Mechanically Assisted Circulatory Support). J Am Coll Cardiol. 2014;63:1751-1757. 6. Slaughter MS, Rogers JG, Milano CA, et al. Advanced heart failure treated with continuous-flow left ventricular assist device. N Engl J Med. 2009;361:2241-2251.

Heartmate 3 : Fully Magnetically Levitated LVAS

481Mehra MR, Naka Y, Uriel N et al. N Engl J Med. 2017 Feb 2;376(5):440-450

Wide blood flow passages to reduce shear stress

Frictionless with absence of mechanical bearings

Intrinsic Pulse designed to reduce stasis and avert thrombosis

• KEY DESIGN FEATURELarge and Consistent Gaps designed to minimize shear stress and blood component activation.

– Secondary flow paths ~0.5 mm along the side, and ~1.0 mm above and below the rotor.

– Pump surfaces flat and flow is undisturbed.

49

ROTOR & MAG-LEVBlood Path with Textured Surfaces

~1.0 MM TOP AND BOTTOM

~0.5 MM ALONG THE

SIDE


• KEY DESIGN FEATURE:Fluid Dynamics designed to minimize shear stress and activation of blood components.

– The HeartMate 3™ rotor and inlet have been designed to minimize shear and avoid stasis over the entire range of operation (2.5 to 10 L/min).

– The relatively large secondary flow paths facilitate smooth flow transitions, generous washing, and low shear.

50


MOMENTUM 3 Study Aims and Endpoints Analyses

Study Aim of the full cohort analysis was to:

• Confirm findings from the earlier pivotal trial cohorts (short-term and long-

term)

• Provide additional statistical power to show superiority for the primary

endpoint

• Power the principal secondary endpoint for pump replacement

Primary Endpoint:

• Survival at 2 years free of disabling stroke (>3 mRS) or reoperation to replace

or remove a malfunctioning device

Principal Secondary Endpoint:

• Pump replacement at 2 years

Other Secondary Endpoints:

• Actuarial survival, rehospitalizations, functional status, and quality of life

Reference: Mehra MR, Uriel N, Naka Y, et al. A Fully Magnetically Levitated Ventricular Assist Device-Final Report. N Engl J Med. 2019 March 17. [Epub ahead of print].

.

Short Term (ST) Cohort1

N=294

6-month follow-up

Randomization

1:1

Patient meets MOMENTUM 3

eligibility criteria?

Long Term (LT) Cohort2

N=366

2-year follow-up

Additional 72

patients enrolled

Full Cohort3

N=1028

2-year follow-up

References: 1. Mehra et al. A Fully Magnetically Levitated Circulatory Pump for

Advanced Heart Failure. N Engl J Med 2017;376(5):440-50. 2. Mehra MR, Goldstein

DJ, Uriel N, et al. Two-Year Outcomes with a Magnetically Levitated Cardiac Pump in

Heart Failure. N Engl J Med. 2018;378(15):1386-1 395. 3. Mehra MR, Uriel N, Naka Y,

et al. A Fully Magnetically Levitated Ventricular Assist Device-Final Report. N Engl J

Med. 2019 March 17. [Epub ahead of print].

Additional 662

patients enrolled

0

6

12

18

24

Month

s o

f F

ollo

w-U

p

Number of Patients294 366 1028

ST cohort

analysisat 6-months1

(7.1%)

LT cohort analysis

at 2-years2

(35.6%)

3rd and final analysis at 2-years (100%)

Full cohort analysis

at 2-years3

(100%)

Year

2015

2016

2017

2018

2019

| ST cohort follow-up complete

| LT cohort follow-up complete

| Full cohort follow-up complete

MOMENTUM 3 : Final Report 2019Study Design and Net Trial Experience

SJM-HM3-0319-0191 | Item approved for Global use.


Baseline CharacteristicsINTERMACS‡ Profile

INTERMACS‡ Profile for MOMENTUM 3 Cohort

HeartMate 3™ LVAD

(N=516)

HeartMate II™

LVAD

(N=512)INTERMACS profile (definition) No. of patients (%) No. of patients (%)

1 Critical cardiogenic shock 11 (2.1) 18 (3.5)

2 Progressive decline on inotropic support 156 (30.2) 146 (28.5)

3 Stable, but inotropic dependent 272 (52.7) 251 (49.0)

4 Resting symptoms 67 (13.0) 82 (16.0)

5-7or not provided*

5-Exertion intolerant

6-Exertion limited

7-Advanced NYHA Class III symptoms

10 (1.9) 15 (2.9)

*Assessments not performed in two (2) HeartMate 3 and five (5) HeartMate II LVAD

patients. SJM-HM3-0319-0191 | Item approved for Global use.


Survival at 2 YearsHeartMate 3™ LVAD continues to show the highest survival for a LVAD at 2 years in a randomized controlled clinical trial

HeartMate II™ LVAD

HeartMate 3™ LVAD


HeartMate 3™ LVAD


Primary Endpoint Met, and Clinical Superiority Demonstrated Event-Free Survival at 2 Years*

* Survival at 2 years free of disabling stroke (>3 mRS) or reoperation to replace or remove a malfunctioning device


HeartMate 3™ LVAD


HeartMate 3™ LVAD

Superiority Analysis

No. at Risk:

HeartMate 3™ LVAD


P <0.0001 by log-rank test

2.3%

11.3%

0%

2%

4%

6%

8%

10%

12%

14%

% P

ati

en

ts w

ith

Pu

mp

R

ep

lac

em

en

t

RR (95%CI) = 0.21 (0.11 – 0.38)

P<0.0001

HeartMate 3

(N=515)

HeartMate II

(N=505)

Powered Secondary End Point AnalysisSignificantly lower rate of pump replacement at 2 years

On ly 3 HeartMate 3™ LVAD ex c hanges for suspected pump

t h rombosis or elevated LDH


Key Adverse Event: Pump ThrombosisSignificantly higher freedom from suspected or confirmed pump thrombosis


HeartMate 3™ LVAD


HeartMate 3™ LVAD

No. at Risk:

On ly 7 c ases out of 515 of suspected or c o nfirmed pump thrombosis (1.4%)

99%FREEDOM FROM PUMP

THROMBOSIS


HeartMate 3™ LVAD


HeartMate 3™ LVAD

Key Adverse Event: StrokeSignificantly higher freedom from all stroke in HeartMate 3™ LVAD than control

Ad verse event rate for stroke: 9.9%


2-yr Stroke Rates in Contemporary Randomized Clinical TrialsHeartMate 3™ LVAD patients had the lowest stroke rates at 2 years

MOMENTUM 3 Full Cohort ENDURANCE

10%

19% 20%25%

12%

30%

0%

5%

10%

15%

20%

25%

30%

35%

40%

HeartMate 3 HeartMate II HeartMate II HVAD HeartMate II HVAD

Surv

ival

(%)

Baseline stroke rate at 2 years with medical management44%

ENDURANCE Supplemental

Stroke Rate at 2 Years inMOMENTUM 31, ENDURANCE Supplemental2, and ENDURANCE3


Results are from different trials, with different cohorts, and cannot be compared directly.References. 1. Mehra MR, Uriel N, Naka Y, et al. A Fully Magnetically Levitated Ventricular Assist Device-Final Report. N Engl J Med. 2019 March 17. [Epub ahead of print]. 2. Markham DW, Pagani FD, Milano CA, et al. Two-year Outcomes in the ENDURANCE Supplemental Trial. Presented at AHA 2018. 3. Rogers JG, Pagani FD, Tatooles AJ, et al. Intrapericardial Left Ventricular Assist Device for Advanced Hear Failure. N Engl J Med. 2017;376:451-60 .

Key Adverse Event: GI BleedingSignificantly higher freedom from GI bleeding in HeartMate 3™ LVAD patients than control


HeartMate 3™ LVAD


HeartMate 3™ LVAD


GI Bleeding Rates in Contemporary Randomized Clinical TrialsHeartMate 3™ LVAD patients had the lowest GI bleeding rates at 2 years

MOMENTUM 3 Full Cohort ENDURANCE

25%31%

45%

39% 34% 35%

0%

5%

10%

15%

20%

25%

30%

35%

40%

45%

50%

HeartMate 3 HeartMate II HeartMate II HVAD HeartMate II HVAD

Surv

ival

(%)

ENDURANCE Supplemental

GI Bleeding Rate at 2 Years inMOMENTUM 31, ENDURANCE Supplemental2, and ENDURANCE3


Results are from different trials, with different cohorts, and cannot be compared directly.References. 1. Mehra MR, Uriel N, Naka Y, et al. A Fully Magnetically Levitated Ventricular Assist Device-Final Report. N Engl J Med. 2019 March 17. [Epub ahead of print]. 2. Markham DW, Pagani FD, Milano CA, et al. Two-year Outcomes in the ENDURANCE Supplemental Trial. Presented at AHA 2018. 3. Rogers JG, Pagani FD, Tatooles AJ, et al. Intrapericardial Left Ventricular Assist Device for Advanced Hear Failure. N Engl J Med. 2017;376:451-60 .

Hospitalization rates and Duration of Hospitalization Significantly fewer days in hospital for HeartMate 3™ LVAD patients than control

Reference: 1. Mehra MR, Salerno C, Cleveland JC, et al. Health Care Resource Use and Cost Implications in the MOMENTUM 3 Long-Term Outcome Study: A Randomized Controlled Trial of a Magnetically Levitated Cardiac Pump in Advanced Heart Failure. Circulation. 2018 May 27. pii: CIRCULATIONAHA.118.035722. doi: 10.1161/CIRCULATIONAHA.118.035722. [Epub ahead of print]. x

66

LVAD:

INDICATIONS AND TIMING

Time to Transition: Clinical Cues

• Repeated (≥2) hospitalizations or ED visits for HF in the past year

• Progressive deterioration in renal function

• Weight loss without other cause (e.g. cardiac cachexia)

• Intolerance to ACE inhibitors due to hypotension and/or worsening renal function

• Intolerance to beta blockers due to worsening HF or hypotension

• Frequent systolic blood pressure < 90 mmHg

• Persistent dyspnea with dressing or bathing requiring rest

• Inability to walk 1 block on the level ground due to dyspnea or fatigue

• Recent need to escalate diuretics to maintain volume status, often reaching daily furosemide equivalent dose > 160 mg/d and/or use of supplemental metolazone therapy

• Progressive decline in serum sodium, usually to < 133 mEq/L

• Frequent ICD shocks

Yancy et al. 2013 ACC/AHA Guideline for the Management of Heart Failure. Circulation June 5, 2013

High-risk clinical triggers for referral for evaluation for advanced heart failure therapies1

Reference: 1. 2017 ACC Expert Consensus Decision Pathway for Optimization of Heart Failure Treatment: Answers to 10 Pivotal Issues About HeartFailure With Reduced Ejection Fraction: A Report of the American College of Cardiology Task Force on Expert Consensus Decision Pathways. Yancy CW, Januzzi JL Jr, Allen LA, Butler J, Davis LL, Fonarow GC, et al. J Am Coll Cardiol. 2018 Jan 16;71(2):201-230.

Review before LVAD Implant

Circulation. 2009; 119: 2225-2232

70

Why patients chose a LVAD?Survival vs Quality Living

Circulation 2012, 125:1928-1952

When late may be too late…

J HeartLungTransplant 2017; 36:1080–1086

INTERMACS PROFILES: LVAD Timing

73

75

LVAD:

FUTURE DIRECTIONS

Future Directions

• Further miniaturization

• Improved Connectivity

• Remote monitoring

• Transcutaneous Transmission ~ 5 yrs

76

HeartMate™ LVAS Equipment Overview

77

Battery Charger:Charges, calibrates, and tests the

batteries.

App and TabletProvides clinicians with the ability to

wirelessly program and monitor system parameters, track alarm

conditions, and view and save data.

Go Gear Wearables:Organizes the System Controller and

batteries for patients to wear and carry.

14 V Li-Ion Batteries and Clips:Power the system when patients are active

or outdoors for up to 17 hours. 2 batteries are used at a time with clips.

Power Module and Wireless Adapter

Provides power to the system from AC outlet and also connects to the System

Monitor via Wireless Adapter.

Mobile Power Unit:Connects to the System Controller to

transfer power from AC outlet.

HM Touch: New Wireless Communication System

Wireless Adapter

HeartMate Touch™ Communication System Introduction

78

Controller

AC Power Supply

External Battery

Controller Power Connector

Battery Charger

HM3 LVAD

Battery Cable

Patient Cable

Controller Cable Edison Driveline

Connection

Edison Percutaneous

Cable

HeartMate™ Touch

Bluetooth

Software Embedded

Future Compatibility -Merlin.Net™

Wearables

Transport

System Overview

79

79

HeartMate Touch™ App

Wireless Adapter

Power Adapter & Apple Travel adapter kit for international markets

Bluetooth®

Wireless Technology

HeartMate Touch™ Communication System

2

Tablet installed in a protective case

1

3

4

5

HeartMate Touch™ Communication System Introduction

External Memory Drive

Next Generation Wearables and Transport Solutions

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Daily Bag

VestBelt

Shower Bag Transport

LVAD: Take Home Points

• Advanced Heart Failure has a poor prognosis without early recognition and treatment

• After survival, functional Status and QOL improvements are Important factors for patients

• LVAD technology has come a long way and continues to evolve with improved durability and side effect profile

• Early patient referral to an advanced center for shared decision making with patients is recommended for optimal outcomes

81

Our future?

82

The Borg: From the Star Trek television series. The Borg represented a hybrid of

humans and machines

Thank you for your Attention

83

lvad update for primary care a bit of past, present and future

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