an equal opportunity university charles hoopes md jason alexander gill professor in thoracic surgery...

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An Equal Opportunity University les Hoopes MD n Alexander Gill Professor in Thoracic Surgery ion Chief, Heart and Lung Transplant/Mechanical Circulatory Support ctor, UK Comprehensive Transplant Center ersity of Kentucky ngton, KY Evolution of Mechanical Circulatory Support – From the Balloon Pump to the Destination Ventricular Assist Device

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Page 1: An Equal Opportunity University Charles Hoopes MD Jason Alexander Gill Professor in Thoracic Surgery Section Chief, Heart and Lung Transplant/Mechanical

An Equal Opportunity University

Charles Hoopes MDJason Alexander Gill Professor in Thoracic SurgerySection Chief, Heart and Lung Transplant/Mechanical Circulatory SupportDirector, UK Comprehensive Transplant CenterUniversity of KentuckyLexington, KY

Evolution of Mechanical Circulatory Support – From the Balloon Pump to the Destination Ventricular Assist Device

Page 2: An Equal Opportunity University Charles Hoopes MD Jason Alexander Gill Professor in Thoracic Surgery Section Chief, Heart and Lung Transplant/Mechanical

An Equal Opportunity University

Evolution of Mechanical Circulatory Support – From the Balloon Pump to the Destination Ventricular Assist Device

Charles Hoopes MDJason Gill Professor in Thoracic SurgerySection Chief, Cardiopulmonary Transplant/Mechanical Circulatory Support Director, UK Transplant CenterUniversity of Kentucky

I have no financial disclosuresI have no financial relationship with any ofthe technologies discussedI will not discuss any off label use of current technologies

Objectives:

Discuss the history of mechanical circulatory support devices from the balloon pump to the first artificial hearts and destination VADs.

Describe the evolution of the mechanical assist device from early conception to today’s current technology in successful treatment of advanced heart therapy.

Describe the clinical implications for implantation of devices and recovery and what issues future devices may solve. 

Page 3: An Equal Opportunity University Charles Hoopes MD Jason Alexander Gill Professor in Thoracic Surgery Section Chief, Heart and Lung Transplant/Mechanical

Conceptual eras of mechanical circulatory support..

Etienne-Jules Marey (Paris,1881) – physician, inventor

.. the 1st “artificial heart

1812 Le Gallois “parts of the body may be preserved by external perfusion”

Guillotined head of a dog in perfusion experiments of Brukhonenko and Tchetchuline. This preparation relied on gas exchange from a second donor dog's lungs. Diaphragm-like pumps pumped blood into the recipient dog's carotid arteries. Dog heads perfused in this manner remained functional for a few hours. (Reprinted from Brukhonenko S, Tchetchuline S. Experiences avec la tete isolee du chien.1.Technique et conditions des experiences. J Physiol Pathol Gen 1929;27:42)

..a “biological oxygenator”

Page 4: An Equal Opportunity University Charles Hoopes MD Jason Alexander Gill Professor in Thoracic Surgery Section Chief, Heart and Lung Transplant/Mechanical

“Experimentally, it is possible to completely replace the heart with an artificial heart, and animals have been known to survive as long as 36 hours. This idea, I am sure, could be reached to full fruition if we had more funds to support more work, particularly in the bioengineering area”DeBakey (1963) Senator Lister Hill’s Subcommittee on Health

Intellectual origins of “mechanical assist” and “circulatory support”…

May 1965 In Jan of 1964 James Hardy consented the sister of Boyd Rush – a 68 yo comatose deaf mute with ischemic heart failure and lower extremity gangrene – for “the insertion of a suitable heart transplant if such should be available. Rush decompensated and was placed on cardiopulmonary bypass. In the absence of a viable donor Hardy transplanted the heart of a 45 kg chimpanzee. The heart provided hemodynamic support for 90 minutes…

“..surgeons at Baylor hailed the Jackson transplant. The Baylor surgeons say there are two solutions for support of the failing heart..transplants from humans or animals and artificial hearts. The Baylor group is concentrating its efforts on developing an artificial heart.”Associated Press, 25 Jan 1964

Page 5: An Equal Opportunity University Charles Hoopes MD Jason Alexander Gill Professor in Thoracic Surgery Section Chief, Heart and Lung Transplant/Mechanical

Ann Review Med 1966

Physiologic basis…

“..mechanical pumping of blood to viscera previously inadequately perfused … reducing the workload and oxygen consumption of the myocardium”

Page 7: An Equal Opportunity University Charles Hoopes MD Jason Alexander Gill Professor in Thoracic Surgery Section Chief, Heart and Lung Transplant/Mechanical

Artificial HeartsFDA Categories of Use in US

(safety and effi cacy)

Post- CardiotomyAbiomedThoratec PVADBiomedicusRoller pumpsECMO

Bridge to TransplantNovacor LVADHeartMate XVE LVADHeartMate IPThoratec PVADsCardioWest Total HeartThoratec I VADsJ arvik LVADMicroMed LVADHeartMate I IMicroMed (Peds)

Bridge to RecoveryThoratec PVADsHeartMate XVEHeartMate I PNovacorMicroMedJ arvik

PermanentHeartMate NovacorMicroMedAbiocorArrow Lionheart

PMA

IDE

Off label

HDE

18 Legal systems8 Off label systems

As medical technology…

Evolution of Mechanical Circulatory Support… HeartWare

Thoratec

Abiomed

Page 8: An Equal Opportunity University Charles Hoopes MD Jason Alexander Gill Professor in Thoracic Surgery Section Chief, Heart and Lung Transplant/Mechanical

Historical context oxygenators and pumps, biological and mechanical

Application (why are you doing this and what do you want)

“moratorium of decision” (non-durable )“bridge to recovery” (non-durable and durable)“bridge to transplant” (non-durable and durable)“destination therapy” (durable)

Deployment (how do we do it and when do we try)

Problems (general, device specific, and evolving)

Evolution of Mechanical Circulatory Support…

As clinical medicine…

Page 9: An Equal Opportunity University Charles Hoopes MD Jason Alexander Gill Professor in Thoracic Surgery Section Chief, Heart and Lung Transplant/Mechanical

Historical “truisms” in mechanical circulatory support (MCS)…

Deployment of MCS technologies in the context of medical futility results in futile deployment of technology… MCS is capable of

resuscitation, not reanimation

MCS technology restores hemodynamics (>86%) but may not alter survival depending upon the specifics of deployment

“Unnecessary surgery” performed well has excellent outcomes…device technology should be deployed based upon clinical trajectory

and the natural history of the disease process

Physiology always trumps engineering..

MCS can support patients awaiting good clinical decision making but is ineffective in supporting bad clinical decisions

Page 10: An Equal Opportunity University Charles Hoopes MD Jason Alexander Gill Professor in Thoracic Surgery Section Chief, Heart and Lung Transplant/Mechanical

3 October 1930 “..at 8AM respirations ceased and the blood pressure could not be obtained.Within 6 min and 30 sec Dr. Churchillopened the chest, incised the pulmonaryartery, extracted a large pulmonary embolus,and closed the incised wound..”

“the idea occurred to me if it were possible to remove continuously some of theblue blood from the patient’s swollen veins, put oxygen into the blood and allow carbon dioxide to escape from it, and then to inject continuously the now red blood back into the patients arteries, we might have saved her life. We would havebypassed the obstructing embolus and performed part of the work of the patients heart and lungs outside the body.”

JH Gibbon

Gibbon JH Jr (1939) The maintenance of life during experimental occlusion of the pulmonary artery followed by survival. Surg Gynecol Obstet 69:604

Page 11: An Equal Opportunity University Charles Hoopes MD Jason Alexander Gill Professor in Thoracic Surgery Section Chief, Heart and Lung Transplant/Mechanical

The original “TandemHeart”…

Dennis et al (1962) Ann Surg 156:623

Page 12: An Equal Opportunity University Charles Hoopes MD Jason Alexander Gill Professor in Thoracic Surgery Section Chief, Heart and Lung Transplant/Mechanical

Pre pLVAD Post pLVAD

Cardiac index, l/(min·m2) 0.52 (0.8) 3.0 (0.9) SBP, mm Hg 75 (15) 100 (15) DBP, mm Hg 30 (20) 65 (20) MAP, mm Hg 45 (20) 81 (15) HR, beats/min 105. 118.0 SVO2, % 49 (11.5) 69.29 (10) PCWP, mm Hg 31.52 17.29 PAP mm Hg 39.16 26.70 Lactic acid, mg/dl 24.5 (74.25) 11.0 (12) LDH, U/dl 602 (630) 416.5 (335) pH 7.22 0.14 7.44 0.06 Urine output, ml/day 70.3 1200 Hemoglobin 11 10.25

The Percutaneous Ventricular Assist Devicein Severe Refractory Cardiogenic Shock

Kar et al (2011) JACC 57:688

Cardiogenic shock: SBP<90mmHg, CI<2 L/min,inadequate end organ perfusion with IABP/pressor support

88 ischemic, 37 non-ischemic (9 myocarditis)

pLVAD (TandemHeart): SVO2>70%, MAP>60mmHg, AoV

DOS 5.8 days…MSOF(n=31),CVA(n=8)

Page 13: An Equal Opportunity University Charles Hoopes MD Jason Alexander Gill Professor in Thoracic Surgery Section Chief, Heart and Lung Transplant/Mechanical

“Pumping improved two patients' circulatory status; one survived. Two patients died before pumping could begin; in another, an abdominal aortic aneurysm prevented insertion of the pump… Kantrowitz et al (1968) JAMA 203:135

Page 14: An Equal Opportunity University Charles Hoopes MD Jason Alexander Gill Professor in Thoracic Surgery Section Chief, Heart and Lung Transplant/Mechanical

RETROSPECTIVE ANALYSIS OF 286 PATIENTS REQUIRING CIRCULATORY SUPPORT WITH THE INTRAAORTIC BALLOON PUMP

Device function must match patient need…preservation of end organ perfusion (survival) and capacity for functional myocardial recovery

The timing of implantation is critical to patient survival…

Mechanical circulatory support (MCS) as a clinical program, not an isolated procedure

“From 1972 through 1974, we implanted the pump in 34 patients. Of those patients, only 2 (1 in 1973 and 1 in 1974) survived until explantation, and only 1 (the patient in 1974) survived to discharge. Yet the intraaortic balloon pump remains essentially unchanged today, and survival rates of 70% to 80% can be expected when the device is implanted in appropriately selected patients … This experience emphasizes the danger of premature randomized studies, which can expose technology to errors that are manmade rather than inherent.”

OH Frazier (2005) Tex Heart Inst J 32:60

Johnson et al (1977) Cardiovasc Dis 4(4):428–436.

Page 15: An Equal Opportunity University Charles Hoopes MD Jason Alexander Gill Professor in Thoracic Surgery Section Chief, Heart and Lung Transplant/Mechanical

Cardiac power is the strongest hemodynamiccorrelate of mortality in cardiogenic shock:A report from the SHOCK trial registry Fincke (2004) JACC 44:340

0.53

CPO: MAP x CO/451

Hemodynamic instability:CI<1.8, CPO<0.53, PCWP>18FiO2/PaO2<300, “high” inotropy

“Escalation therapy” criteria and MCS application…and deployment

Page 16: An Equal Opportunity University Charles Hoopes MD Jason Alexander Gill Professor in Thoracic Surgery Section Chief, Heart and Lung Transplant/Mechanical

Ben Roe and the UCSF “artificial heart” circa 1970

post LVAD

Page 17: An Equal Opportunity University Charles Hoopes MD Jason Alexander Gill Professor in Thoracic Surgery Section Chief, Heart and Lung Transplant/Mechanical

Heartware (impellar)

Heartmate II (axial flow)AbioCor TAH

Syncardia TAH

Left ventricular assist vs.biventricular replacement…

Durable vs non-durable applications

Page 18: An Equal Opportunity University Charles Hoopes MD Jason Alexander Gill Professor in Thoracic Surgery Section Chief, Heart and Lung Transplant/Mechanical

I II III

Evolution of implantable mechanical cardiac assist technologies……

Page 19: An Equal Opportunity University Charles Hoopes MD Jason Alexander Gill Professor in Thoracic Surgery Section Chief, Heart and Lung Transplant/Mechanical

The complexity of mechanical circulatory support technologies represents…

epidemiology…a significant clinical need…cardiogenic shock is highly morbid and frequently lethal (>55%)

absence of a common effective therapy… anecdotal experience not supported by clinical trials pkVO2

12-16 ml/kg/min

variability of clinical application…

“Crash and burn” will get bridge to durable device

Ongoing RCT in low risk pts with pkVO2 12-16 ml/kg/min

Inotrope dependent

1. Critical cardiogenic shock 2. Progressive decline 3. Stable inotrope dependent 4. Recurrent advanced disease 5. Exercise intolerant 6. Exercise limited 7. Advanced NYHA class III

Page 20: An Equal Opportunity University Charles Hoopes MD Jason Alexander Gill Professor in Thoracic Surgery Section Chief, Heart and Lung Transplant/Mechanical

Risk factors for death in patients with an implantable mechanical circulatory support device:

older patient age at the time of implant (relative risk [RR] = 1.41, p < 0.001);

assignment to INTERMACS Level 1 category characterized by cardiogenic shock with life-threatening hypoperfusion (RR = 1.59, p = 0.02);

indicators of severe right ventricular failure, such as ascites and hyperbilirubinemia, which are clinically evident at the time of implant

Pagani et al (2009) J Heart Lung Transpl

Page 21: An Equal Opportunity University Charles Hoopes MD Jason Alexander Gill Professor in Thoracic Surgery Section Chief, Heart and Lung Transplant/Mechanical

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Months after Device Implant

Competing Outcomes – Level 1: Critical Cardiogenic Shock (n=186)

Transplanted 40%

Dead 29%

Alive 26%Recovery 5%Pr

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Competing Outcomes – Level 2: Progressive Decline (n=148)

Months after Device Implant

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Competing Outcomes – Level 3: Stable but Inotrope Dependent (n=35)

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INTERMACS

Page 22: An Equal Opportunity University Charles Hoopes MD Jason Alexander Gill Professor in Thoracic Surgery Section Chief, Heart and Lung Transplant/Mechanical

Evolution of mechanical circulatory support…ventricular assist devices

Slaughter M (2010) Will destination therapy be limited to large transplant centers? Texas Heart Inst J 37(5):562

Moratorium of decisionBridge to recoveryBridge to transplantDestination (CMS)

Are VADs an operation…or part of an integrated heart failure program?

Page 23: An Equal Opportunity University Charles Hoopes MD Jason Alexander Gill Professor in Thoracic Surgery Section Chief, Heart and Lung Transplant/Mechanical

No device has ever saved or killed a patient … good physicians using good devices have done both

No device program has everything … effective device programs have everything they need

Device technology accomplishes nothing but facilitates everything

The evolution of mechanical cardiopulmonary support …the “learning curve”

Page 24: An Equal Opportunity University Charles Hoopes MD Jason Alexander Gill Professor in Thoracic Surgery Section Chief, Heart and Lung Transplant/Mechanical

May ‘08

Dec ‘08

LVAD induced remodeling: Basic science and clinical implications for recovery

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Pre-explant(12)

Inotrope dependent

Feb ‘09s/p LVAD

LVADDec ‘08

* biomarkers of recovery (genetic,structural,metabolic)

* therapeutic intervention (pre,post,and peri)* etiology of CHF (sequential tissue)

Leftward shift of the EDPVR(structural “reverse remodeling”)

Time dependent reduction in heart size (EDP of 30 mmHg, V30)

Regression of cellular hypertrophy

Page 25: An Equal Opportunity University Charles Hoopes MD Jason Alexander Gill Professor in Thoracic Surgery Section Chief, Heart and Lung Transplant/Mechanical

May ‘08

Dec ‘08

LVAD induced remodeling: Basic science and clinical implications for recovery

Inotrope dependent

Feb ‘09

s/p LVAD

LVAD

Dec ‘08

Leftward shift of the EDPVR (structural “reverse remodeling”)

Time dependent reduction in heart size (EDP of 30 mmHg, V30)

Regression of cellular hypertrophy