Future is in Assist Device

Nir Uriel MD

Associate Professor of Medicine

Medical Director of Heart Failure, Heart Transplant and

Mechanical Circulatory Support Program

University of Chicago

ACC March 2015

California

2

3

King Jon Kobashigawa the 1st

4

1st Heart Transplantation

Professor Christiaan Barnard performed the first human heart transplant on the third of December 1967

Figure 10

The Journal of Heart and Lung Transplantation 2014 33, 996-1008DOI: (10.1016/j.healun.2014.08.003) The Journal of Heart and Lung Transplantation 2014 33, 996-1008DOI: (10.1016/j.healun.2014.08.003)

Excellent Post Transplant Survival

The Prevalence of Heart Failure

• Estimated 23 million people with HF worldwide

• United States: 5.8 million

3.1 million men, 2.7 million women

• 670 000 cases diagnosed each year with over 1 million

hospitalizations and 3.4 million outpatient visits

• The healthcare cost of HF is estimated at $39.2 billion in the United

States for 2010

Prevalence of Common Cardiovascular and Lung Diseases, U.S., 2004, NHLBI report Death from specific cardiovascular, Lung and Blood Diseases, U.S., 2004 NHLBI report

The population of these patients is large: In the US,

~300K AHF patients

~240 M US Population ≥ 20 years old

6.24 M HF = 2.6% of the population

3.12 M Systolic HF = 50% of HF population

124,800 Adv. Stage C / NYHA IIIB Advanced Stage C = 3-4%

156,000 Stage D / NYHA IV =

0.5-5%

70,200 25% Accessible AHF Patients

30 Patients / 100,000 Population

Potential VAD / TX patient population - National

117 Patients / 100,000 Population

AHF Patients:

Potential VAD / TX Patients:

Incidence: 7 / 100,000 each year

Heart Transplants in Major Metropolitan Statistical

Areas (2010)

MSA Population Transplants Per 100,000

New York 21,976,224 110 0.5

Los Angeles 17,775,984 143 0.8

Chicago 9,725,317 76 0.8

Philadelphia 6,382,714 98 1.5

Houston 5,641,077 107 1.9

Total 61,501,316 534 0.9

Figure 1

The Journal of Heart and Lung Transplantation 2014 33, 996-1008DOI: (10.1016/j.healun.2014.08.003)

Heart Transplant Not for Every One

UNOS Status

Transplanted

in status Median

waiting time

1A

1B

2

64%

31%

5%

78 days

224 days

618 days

Stehlik J, Stevenson LW, Mehra MR et al. JHLT Oct 2014.

Median Waiting Time to Transplant

Jon Kobashigawa MD , 14 October 2014:

“The marginal donors of a few years ago are our standard donors

today”

!

US Dept of HHS Scientific Registry of Transplant Recipients srtr.transplant.hrsa.gov

Death or delisting due to progressive illness while on wait-list: 18%

2008

BTT – Survival to Transplantation

150 HM II BTT on UNOS list (1A or 1B) survival compared to medically managed

– BTT older with more co-morbidities

Trivedi et al An Thorac Surg 2014 epub

Heart Transplantation

Heart Transplant as a Solution?

18

LVAD – a New Heart Physiology

Decompression of the Heart

UP Jorde et al Journal of the American College of Cardiology, Volume 63, Issue 17, 2014, 1751 - 1757

Current Status DT for Advanced Heart Failure

improvement with the HeartMate (HM) II continuous-flow LVAD

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011

Total Adult Cardiac Transplants w Device

LVAD Bridged De Novo

Uriel N et al. J Heart Lung Transplant. 2013 Feb;32(2):188-95

The Number of LVAD BTT from the Total OHT is Increasing

Functional Status – 6 Minute Walk

0

50

100

150

200

250

300

Baseline 1 mo 3 mo 6 mo

LVAD Duration

Mete

rs

271 235 175 128

30 + 88

166 + 168

244 + 218

285 + 235

Pagani F et al. JACC: Vol 54, No 4, 2009.

Functional Status – NYHA Class I or II

0

10

20

30

40

50

60

70

80

90

100

Baseline 1 mo 3 mo 6 mo

LVAD Duration

Perc

en

t o

f p

ati

en

ts

NYHA II

NYHA I

59%

83% 82%

0%

259 213 169 120

Pagani F et al. JACC: Vol 54, No 4, 2009.

U.S. Chronic VAD Implants vs. Heart Transplants, 2009-2013

Projected U.S. Chronic VAD implants by Indication (Analyst Estimates), 2014-2018

131 Destination Therapy centers in the US today

~3,900

~3,400

~2,750

~2,150~1,850

~2,500~2,400~2,300~2,200~2,150

2013 2012 2011 2010 2009

2,074 2,081 2,127

1,999 2,2862,638

3,1093,856

2,1632,158

4,765

2018 2016

5,268

6,018

2015

4,367

2014

4,073

2017

Transplants

VADs CAGR

10%

18%

1%

BTT

DT

Adverse Events

Uriel et al. Jour Am Col of Card. 2010;56(15):1207-1213. Garan AR…..Uriel N et al. J Am Coll Cardiol. 2013 May 2

Jorde UP, Uriel N, Circ HF 2014 Uriel N et al. JHLT 2014

Expensive

28

Fang JC. N Eng J Med. 2009 Dec 3;361(23):2282-5 Schwarzenegger A…Cameron J. Terminator 3: Rise of the Machines 2003

• “left on vacation to celebrate 50th anniversary, we went to Paris 1st, the flew to Istanbul

where …..we were away for 18 days and had a great time! How’s that for a medical

miracle?”

30

Jarvick 2000

HeartMate III

HeartMate III

Designed to be Hematologically-Compatible

Leverages Fully Magnetically Levitated Technology

Features

•Fully Magnetically Levitated

•Large pump gaps designed to reduce blood trauma

•Artificial pulse

•Textured blood contacting surfaces

•Wide range of operation

•Full support (2 – 10 L/min)

• Advanced Design for Surgical Ease

•Engineered apical attachment

•Modular Driveline

•Pocket Controller

MVAD

Circulite – NYAH class III?

Circulite

Successful Pregnancy

Sims D et al. J Heart Lung Transplant. 2011 Sep;30(9):1065-7.

37

Survival After Explant

Age at Transplant

Years alive after

Age at Death

20 15-25 35-45

25 15-25 40-50

30 15-25 45-55

40 15-25 55-65

Transplant

Average follow-up of 1172 ± 948 days All patients NYHA Class I

Frazier OH, JHLT 2014

LVAD

Future of Heart Failure – Regeneration

• Combination of Assist device with:

– Stem cell

– Gene expression

– Metabolic alteration

Jon is Living in a Movie

40

Thank you !!

• EMERG group

41 Presentation Title Here |

Our Advanced Heart Failure Team

Destination therapy will drive the growth of the chronic VAD market U.S. Chronic VAD Implants vs. Heart

Transplants, 2009-2013

Projected U.S. Chronic VAD implants by Indication (Analyst Estimates), 2014-2018

131 Destination Therapy centers in the US today

~3,900

~3,400

~2,750

~2,150~1,850

~2,500~2,400~2,300~2,200~2,150

2013 2012 2011 2010 2009

2,074 2,081 2,127

1,999 2,2862,638

3,1093,856

2,1632,158

4,765

2018 2016

5,268

6,018

2015

4,367

2014

4,073

2017

Source: Thoratec Estimates August 2014; OPTN; Average analyst projections for VAD market (Wells Fargo, Goldman, Credit Suisse, BAML) r©2014 Thoratec Corporation. All rights reserved. US-HM2-07140015(1) )

Transplants

VADs CAGR

10%

18%

1%

BTT

DT

We Need Pulsatility?

LVAD speed

Mitral

Regurgitation LVEDD revolutions/min cm

LVAD implant 8,600 Moderate 6.6

Week 13 and 6 days 9,000 Moderate-Severe 5.4

Week 21 and 6 day 9,400 Moderate 5.8

Week 25 and 6 days 9,400 Severe 6.3

Week 26 and 0 days 9,600 Moderate 5.8

Week 32 and 0 days 9,800 Moderate 6.0

Pregnancy Course (Hemodynamics)

UP Jorde et al Journal of the American College of Cardiology, Volume 63, Issue 17, 2014, 1751 - 1757

Results of the DT Post-FDA Approval Study With a Continuous Flow LVAD:

A Prospective Study Using the INTERMACS Registry (Interagency Registry

for Mechanically Assisted Circulatory Support)

Survival of UNOS Status IA: VAD v Inotropes (N=5230)

Waiting List Survival Post Transplant Survival

Wozniak et al Ann Thorac Surg 2013