Michael A. Samara, MD, FACC

Advanced Heart Failure Therapies Cardiac Transplantation and Mechanical Circulatory Support

Advanced Heart Failure/Transplant/Mechanical Circulatory Support Minneapolis Heart Institute at Abbott Northwestern Hospital Part of Allina Health Minneapolis, MN

Innovation Summit 2014 September 26, 2014

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Heart Failure: The Final Cardiovascular Disease

CORONARY DEATH

Deaths/100,000 population

HEART FAILURE

Prevalence/100,000 population

National Hospital Discharge Survey Data. Centers for Disease Control and Prevention National Center for Health Statistics and National Heart, Lung, and Blood Institute

1980 1990 2000 1980 1990 2000

Improved survival in other CV diseases has led to expansion of the HF Population.

Surv

ival

(%)

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Time (months) J Heart Lung Transplant 2011;30:402–7

Advanced Heart Failure is Cardiac Cancer

Stage IV Pancreatic Cancer

NYHA FC IV (Medical Therapy)

NOTE: This figure includes only the heart transplants that are reported to the ISHLT Transplant Registry. As such, the presented data may not mirror the changes in the number of heart transplants performed worldwide

ISHLT 2011

J Heart Lung Transplant. 2011 Oct; 30 (10): 1071-1132

Heart Transplantation Survival by Era

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Surv

ival

(%)

Years

1982-1992 (N = 25,138) 1993-2002 (N = 37,193) 2003-6/2010 (N = 24,021)

HALF-LIFE 1982-1992: 8.5 years; 1993-2002: 10.9 years; 2003-6/2010: NA

1982-1992 vs. 1993-2002: p < 0.0001 1982-1992 vs. 2003-6/2010: p <0.0001 1993-2002 vs. 2003-6/2010: p <0.0001

1-year 94% 3-year 90%

MHI at ANW

~ 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

374,400 Stage C/D

NYHA IIIb-IV

93,600 Target VAD/Tx Population

Projected Advanced HF Therapy Population

1 US Census Bureau Statistics (2007) 2 Heart and Stroke Statistics, American Heart Association

3 Cardiovascular Round Table research and analysis, The Advisory Board company (2009)

280,800 Disqualifying Comorbidities

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There are currently approximately

100,000 potential candidates in the

United States.

Likely several hundred in the Allina System.

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NOTE: This figure includes only the heart transplants that are reported to the ISHLT Transplant Registry. As such, the presented data may not mirror the changes in the number of heart transplants performed worldwide.

Heart Transplant Volumes Reported by Year

ISHLT 2011

J Heart Lung Transplant. 2011 Oct; 30 (10): 1071-1132

U.S. Chronic VAD Implants vs. Heart Transplants, 2007-2012

Projected U.S. VAD implants by Indication (Estimates), 2013-2016

~1,325

~1,850 ~2,150

~2,750

~3,400

~2,200 ~2,150 ~2,200 ~2,300 ~2,300

2012 2010 2009 2008 2007

2,233

3,702

2016

5,935

2013 2015

5,089

2,193

2,895

2014

4,468

2,103

2,365

3,906

1,993

1,914

Source: Thoratec Estimates; Average analyst projections for VAD market (Wells Fargo, JP Morgan, Credit Suisse, Oppenheimer)

VADs Transplants

VAD Implants have Already Surpassed Transplant Volumes

Bridge to Transplant Destination

Indications • Post-cardiotomy Shock • Acute Myocardial Infarctions • Cardiac Arrest • Acute on chronic decompensated systolic heart failure • Acute fulminant myocarditis Why Early Application of MCS Makes Sense • Decompress the ventricle(s) •  Lung protection • Wean off toxic levels of inotropes/pressors • Correct metabolic derangements • Preserve end-organ function

Cardiogenic Shock

Venoarterial Extracorporeal Membrane Oxygenation

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Total Patients

Survived ECLS (%) Survived to

Discharge (%)

Respiratory 5,146 3,317 64% 2,905 56%

Cardiac 4,042 2,255 56% 1,636 40% ECPR 1,238 476 38% 355 29%

Expanding Use of Extracorporeal Life Support

65%

SHOCK TEAM •  Interventional Cardiologist •  Heart Failure Cardiologist •  Intensivist •  Cardiothoracic Surgeon •  Vascular Surgeon •  ICU Nurse •  Perfusionist

RAPID TRIAGE AND INITIATION •  Performed in cath lab •  Rapid assessment of

hemodynamics •  20% of patients with ongoing

CPR at time of cannulation

ETIOLOGY OF REFRACTORY

FAILURE

CARDIO-PULMONARY

Pulmonary + RV

RA-LA ECMO

Pulmonary + LV/BiV

VA ECMO

CARDIAC

RV Failure pRVAD

LV Failure pLVAD

BiV Failure pRVAD/pLVAD

PULMONARY VV ECMO

Tailored Approach to Temporary MCS in Refractory Failure

• Centrimag • Rotaflow

• Centrimag • Rotaflow

• Centrimag • Rotaflow

• Centrimag • Rotaflow • Tandem • PVAD

• Impella 5 • Tandem • PVAD

• Tandem • PVAD

• Bridge to Transplant*: Inserted for short to intermediate term support in patients actively listed for transplant

• Destination Therapy*: Inserted with the intention of long term support in patients who are not transplant candidates

• Bridge to Recovery: Inserted for short term support in a condition that is anticipated to reverse (e.g., fulminant myocarditis, EtOH cardiomyopathy, etc.)

• Bridge to Decision: Inserted for support when ultimate therapy is not able to be determined at the time of implantation

Defined Indications for Durable VADs

*only designations currently recognized by regulatory/payor community ~20% crossover in clinical trials (BTT!"DT)

•  >18,000 implants

•  Axial continuous-flow from LV to ascending aorta

•  Easy surgical implantation •  Smaller pre-peritoneal pocket

•  Electrically powered •  Batteries & line power

•  Silent, vibration-free operation •  Flow range: 3-10 L/min

•  Designed for extended durability with single moving part

HeartMate II® LVAD

Summary of HeartMate II ® BTT Outcomes

Reference Study Enrollment period n Survival at 180

days Miller, Pagani, Russell et al NEJM 357:885-896, 2007

HM II Pivotal Trial 3/05- 5/06 133 79%

Pagani, Miller, Russell et al JACC 54:312-321, 2009

HM II Pivotal Trial 3/05- 3/07 281 84%

Starling, Naka, Boyle et al JACC 57:1890-1898, 2011

Post Approval Study 4/08 – 8/08 169 91%

Summary of HeartMate II® Destination Therapy Outcomes

Reference Study Enrollment period n

One-Year Survival

Two-Year Survival

Slaughter, Rogers, Milano et al NEJM 2009;361:2241-51.

HM II Pivotal Trial 3/05- 5/07 134 68% 58%

Park, S et al Circ Heart Failure 2012;5:241-8.

HM II Pivotal Trial 5/07- 3/09 311 74% 64%

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Baseline 1 mo 3 mo 6 mo

Met

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JAAC 2009;54(4):312-21.

HeartMate II® BTT Trial Improvement in 6-minute Walk and NYHA Class

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Baseline 1 mo 3 mo 6 mo

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NYHA II

NYHA I

59%

83% 82%

0%

NYHA Functional Class 6-minute Walk

1.  J Amer Coll Cardiol. 2011;57(19):1890-1898. 2.  Stroke. 2006;37(2):562-571. 3.  Two-Year Outcomes in the Destination Therapy Post-FDA-Approval Study with a Continuous Flow Left Ventricular Assist Device: A Prospective

Study Using the INTERMACS Registry. U.P. Jorde, S.S. Kushwaha, A.J. Tatooles, et al. Presented at the ISHLT annual meeting, April 25, 2013.

Device Related Infection

Bleeding Requiring Surgery

Pump Replacement

Isc Stroke Hem Stroke Hemolysis Thrombus

Trial Post-Approval Study

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0.031

0.47

0.22 0.07

0.052

0.024

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0.024 0.027

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0.057

0.026

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yea

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Note: 3x scale difference for Device infection and Bleeding requiring surgery compared to others

. . . Since the trial adverse event occurrence continues to decline3

HeartMate II® BTT Trial Adverse Event Rates are Falling with Clinical Experience

Heartware HVAD® Centrifugal/Radial Flow LVAD

J Am Coll Cardiol. 2011;57(12):1375-1382

Circulation. 2012;125:3191-3200

Aorta LV apex

•  Centrifugal pump with hybrid magnetic/hydrodynamic impeller suspension "

•  3,500 implants worldwide

•  Approved for use in EU in January 2009

•  FDA approved for BTT only in US

HeartWare® System

Small pump attaches directly to the heart

Thin, flexible driveline cable exits skin

A small controller & batteries run the pump

CAUTION:  Federal  Law  (USA)  restricts  this  device  to  sale  by  or  on  the  order  of  a  physician.    Refer  to  the  “Instructions  For  Use” for complete Indications for Use, Contraindications, Warnings, Precautions, Adverse Events and Instructions prior to using this device.

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68%

58% 55%

24%

8%

23%

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52%

NEJM 2001; 345:1435-43 NEJM 2009; 361:2241-2251

Continued Stepwise Improvement in Survival in Clinical Trials

OMM Rose 2001

XVE DT Slaughter 2009 XVE DT Rose 2001

HMII DT Slaughter 2009

HMII BTT Pagani 2009

Heartware BTT 2013

88%

75% ~90% 1-year survival in Bridge to Transplant Patients* ~70% 1-year survival in Destination Therapy Patients*

Total Artificial Heart

Inlet Cannula in Left Atrium

Pump to the Subclavian Artery

Subcutaneous pump implanted like a pacemaker

CircuLite®: A Permanent, Partial Support LVAD with Minimally Invasive Implantation

European Journal of Cardio-thoracic Surgery, 39 (2011) 693-698.

Can early, partial support alter the natural history of

advanced HF?