rogers advances in advanced heart failure therapies...

Duke Heart Center

Joseph G. Rogers, M.D.Associate Professor of MedicineSenior Vice Chief for Clinical Affairs, Division of CardiologyMedical Director, Cardiac Transplant and Mechanical Circulatory Support ProgramDuke University

Advances in Advanced Heart Failure Therapies

9th Annual Dartmouth Conference on Advancesin Heart Failure Therapies

Dartmouth-Hitchcock Medical CenterMay 20, 2013

Duke Heart CenterDuke Heart Center

Disclosures

Consultant: Thoratec Corporation

Principal Investigator, HeartWare ENDURANCE trial


Management Algorithm for Patients in Cardiogenic Shock

Rogers JG, Milano CA , The role for mechanical support in cardiogenic shock, AHA Publication, 2009


The Problem of Acute Cardiogenic Shock

New Engl J Med 2012;367:1287-96

IABP SHOCK II Trial

On the basis of the IABP-Shock II trial, we must move forward with the understanding that a cardiovascular condition with a 40% mortality at 30-days is unacceptable.

New Eng J Med 2012;367:1349-50


Novel Mechanical Approaches to Treat Acute Cardiogenic Shock

Need controlled clinical trials of novel mechanical circulatory assist devices for acute heart failure


TandemHeart in Cardiogenic Shock: THI Experience

118 patients with refractory cardiogenic shock Nearly 50% had just received or were receiving CPR Mean support duration = 5.8 days

J Am Coll Cardiol 2011;57:688-96

Am Heart J 2006;152:469

Artificial Organs 2006;30: 523-8


Mechanical Right Heart Support

Two limbs in trial:1) Post MI RV failure; 2) Post heart surgery


The Stage D Heart Failure Patient

• 5% of the heart failure population

• Intolerable symptoms• Frequent hospitalizations• Limited therapeutic options

0.00

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0 6 12 18 24 30 36 42 48 54Months Post Enrollment

Pe

rce

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rviv

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N Engl J Med 2001; 345:1435-43

Advanced Heart Failure Decision Making

Advanced HF SymptomsSevere LV Dysfunction

Standard Therapies Utilized

Pt wishes to proceedViable candidate

Yes No

Palliative CareHospice

Management of Co-morbiditiesTailored Medical Therapy/PAC

Suitable improvement

Yes

Continue

No

Continuous infusion inotropes

LVAD Transplant

Duke Heart Center

Impact of Inotropes on Survival

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100

0 3 6 9 12

Mo on Inotropic Therapy

Mo

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(%)

Placebo

Randomized IV Inotropes

Uncontrolled IV Inotrope

Oral Milrinone Class IV

REMATCH InotropeDependent

Oregon Series

Circulation 2003; 108:492-97


NUMBER OF HEART TRANSPLANTSBY YEAR AND LOCATION

J Heart Lung Transplant. 2012 Oct; 31(10): 1045-1095


ADULT HEART TRANSPLANTSPatients Bridged with Mechanical Circulatory Support*

(Transplants: January 2000 – December 2010)

* LVAD, RVAD, TAH



HEART TRANSPLANTSKaplan-Meier Survival

(Transplants: January 1982 - June 2010)

N = 96,273N at risk at 25 years = 112



ADULT HEART RECIPIENTS Functional Status of Surviving Recipients

(Follow-ups: January 2000 – June 2011)



VAD Implantation in the US

J Heart Lung Transplant 2013;32:141-56


Mechanically Assisted Circulation: Contemporary Devices

Continuous Flow PumpsFlow Characteristics: continuousValves: noOperating Mode: fixed speed

Continuous Flow PumpsFlow Characteristics: continuousValves: noOperating Mode: fixed speed

Axial Flow Pump Centrifugal Flow Pump

Mechanically Assisted Circulation: Contemporary Devices and Outcomes

Months

0 3 6 9 12

Pe

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rviv

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P < 0.001 log-rank test

Post-Trial (N=1496)

Trial (N=486)76%

85%

Bridge to Transplant

Ann Thorac Surg 2011;92:1406-13

Time (Months)

0 6 12 18 24

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10

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30

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50

60

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90

100

Mid trial (N=281)

Early trial (N=133)

74 ± 3%

68 ± 4%

64 ± 3%

58 ± 4%

At Risk:

281133

21595

18882

16769

9462

P(log-rank) = 0.134P(adjusted for BSA) = 0.162

Average Support Duration

Early trial = 2.0 ± 1.6 years (longest: 5.5 years)

Mid trial = 1.5 ± 1.0 years (longest: 3.4 years)

Destination Therapy

Circ Heart Failure 2012;5:241-8

Bridge to Transplant

Circulation 2012;125:3191-3200

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I I I I I

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IV

J Am Coll Cardiol 2010; 55: 1826-34J Am Coll Cardiol 2010; 55: 1826-34

6 MIN WALKNYHA CLASS

KCCQ


REVIVE-IT ROADMAP

Sponsor NIH, Thoratec Thoratec

Design Randomized Non-randomized

N 100 200

Follow-up Duration (mo) 24 24

Current VAD indication No Yes

10 Endpoint Survival free from disabling stroke and

increased 6MWD ≥ 75 m at 24 months

Survival with increased 6MWD ≥75 m at 12 months

LVEF ≤ 0.35 ≤ 0.25

NYHA Class III IIIb-IV

6 min Walk ≤ 350 meters <300 meters

Ongoing trials using MCS in non-inotrope dependent, ambulatory heart failure


Innovations in Mechanical Circulatory SupportFocus on enhanced durability, biocompatibility, energy efficiency and

less invasive implant techniques

New Devices Totally Implantable


VADS for Partial Support

Circulite Synergy• Surgical or percutaneous implant• Partial cardiac assist• Flow 2-3 l/min• Modeling suggests reduction of

LVEDP 7-10 mm Hg• 8-12 hours of untethered support

Eur J Cardiothorac Surg 2011;39:693-8


Proximal Aortic Counterpulsation

Curr Heart Fail Report 2010;7:27-34


Total Artificial Heart

New Engl J Med 2004;351:859-867

Bridge to Transplant vs Medical Therapy


Strategies for BiVentricular Support

30-day survival 82%

Circulation 2011; 124 (suppl1):s179-s186


N Engl J Med 2006;355:1873-84

Myocardial Functional Recovery on a Pulsatile Device: The Harefield Experience

Adjunctive ClenbuterolAdjunctive Cell Therapy

Allogeneic Stem Cells


Duke Heart CenterDuke Heart CenterLancet 2011; 378:1847-57

• 16 patients with ischemic cmy, LVEF < 0.40• 1 million autologous cardiac stem cells administered IC


Tissue Re-Engineering

Taylor DA Texas Heart Inst J 2009 36:148-9


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% P

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nts

6 Mo- 3 Mo

3 Mo- 1 Mo

1 Mo- 3 Days

3 Days-Death

Pain Confusion Dyspnea

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6 Mo-3 Mo 3 Mo-1 Mo 1 Mo-3 Days

% P

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nts

Prefers comfort care

Prefer DNR

J Am Geriatr Soc 48:S101


Summary and Conclusions

Advanced heart failure is associated with high residual morbidity and mortality despite contemporary medical and electrical therapies

Acute cardiogenic shock requires a more innovative and evidence-based approach

Transplant remain the gold standard (MCS takes bronze)

New devices will be smaller, energy efficient and will be implanted with less invasive techniques

The totally implantable systems may significantly reduce morbidty and improve quality of life

Clinical trials for biventricular support are needed

Stem cells remain the holy grail of heart failure therapy

It is imperative that we understand how to utilize palliative care and hospice in heart failure

rogers advances in advanced heart failure therapies...

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