Evolution of Mechanical Circulatory Support From the Balloon

Evolution of Mechanical Circulatory Support – From the Balloon Pump to the Destination Ventricular Assist Device Charles Hoopes MD Jason Alexander Gill Professor in Thoracic Surgery Section Chief, Heart and Lung Transplant/Mechanical Circulatory Support Director, UK Comprehensive Transplant Center University of Kentucky An Equal Opportunity University � Lexington, KY

Evolution of Mechanical Circulatory Support – From the Balloon Pump to the Destination Ventricular Assist Device 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. I have no financial disclosures I have no financial relationship with any of the technologies discussed I will not discuss any off label use of current technologies Charles Hoopes MD Jason Gill Professor in Thoracic Surgery Section Chief, Cardiopulmonary Transplant/Mechanical Circulatory Support Director, UK Transplant Center An Equal Opportunity University � University of Kentucky

Conceptual eras of mechanical circulatory support. . 1812 Le Gallois “parts of the body may be preserved by external perfusion” Etienne-Jules Marey (Paris, 1881) – physician, inventor . . the 1 st “artificial heart 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”

Intellectual origins of “mechanical assist” and “circulatory support”… “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” De. Bakey (1963) Senator Lister Hill’s Subcommittee on Health May 1965 “. . 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 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…

Physiologic basis… “. . mechanical pumping of blood to viscera previously inadequately perfused … reducing the workload and oxygen consumption of the myocardium” Ann Review Med 1966

Evolution of Mechanical Circulatory Support… 1936 1965 1969 1981 1982 1968 As socio-political history…

Evolution of Mechanical Circulatory Support… Heart. Ware Thoratec Abiomed As medical technology…

Evolution of Mechanical Circulatory Support… 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) As clinical medicine…

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

3 October 1930 “. . at 8 AM respirations ceased and the blood pressure could not be obtained. Within 6 min and 30 sec Dr. Churchill opened the chest, incised the pulmonary artery, extracted a large pulmonary embolus, and closed the incised wound. . ” JH Gibbon “the idea occurred to me if it were possible to remove continuously some of the blue 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 have bypassed the obstructing embolus and performed part of the work of the patients heart and lungs outside the body. ” Gibbon JH Jr (1939) The maintenance of life during experimental occlusion of the pulmonary artery followed by survival. Surg Gynecol Obstet 69: 604

The original “Tandem. Heart”… Dennis et al (1962) Ann Surg 156: 623

The Percutaneous Ventricular Assist Device in Severe Refractory Cardiogenic Shock Cardiogenic shock: SBP<90 mm. Hg, CI<2 L/min, inadequate end organ perfusion with IABP/pressor support 88 ischemic, 37 non-ischemic (9 myocarditis) p. LVAD (Tandem. Heart): SVO 2>70%, MAP>60 mm. Hg, Ao. V DOS 5. 8 days…MSOF(n=31), CVA(n=8) Cardiac index, l/(min·m 2) SBP, mm Hg DBP, mm Hg MAP, mm Hg HR, beats/min SVO 2, % PCWP, mm Hg PAP mm Hg Lactic acid, mg/dl LDH, U/dl p. H Urine output, ml/day Hemoglobin Pre p. LVAD Post p. LVAD 0. 52 (0. 8) 75 (15) 30 (20) 45 (20) 105. 49 (11. 5) 31. 52 39. 16 24. 5 (74. 25) 602 (630) 7. 22 0. 14 70. 3 11 3. 0 (0. 9) 100 (15) 65 (20) 81 (15) 118. 0 69. 29 (10) 17. 29 26. 70 11. 0 (12) 416. 5 (335) 7. 44 0. 06 1200 10. 25 Kar et al (2011) JACC 57: 688

“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

RETROSPECTIVE ANALYSIS OF 286 PATIENTS REQUIRING CIRCULATORY SUPPORT WITH THE INTRAAORTIC BALLOON PUMP Johnson et al (1977) Cardiovasc Dis 4(4): 428– 436. 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

“Escalation therapy” criteria and MCS application…and deployment Hemodynamic instability: CI<1. 8, CPO<0. 53, PCWP>18 Fi. O 2/Pa. O 2<300, “high” inotropy CPO: MAP x CO/451 0. 53 Cardiac power is the strongest hemodynamic correlate of mortality in cardiogenic shock: A report from the SHOCK trial registry Fincke (2004) JACC 44: 340

Ben Roe and the UCSF “artificial heart” circa 1970 post LVAD

Left ventricular assist vs. biventricular replacement… Durable vs non-durable applications Heartware (impellar) Syncardia TAH Heartmate II (axial flow) Abio. Cor TAH

Evolution of implantable mechanical cardiac assist technologies… … I II III

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 pk. VO 2 12 -16 ml/kg/min variability of clinical application… 1. 2. 3. 4. 5. 6. 7. Critical cardiogenic shock Progressive decline Stable inotrope dependent Recurrent advanced disease Exercise intolerant Exercise limited Advanced NYHA class III “Crash and burn” will get bridge to durable device Inotrope dependent Ongoing RCT in low risk pts with pk. VO 2 12 -16 ml/kg/min

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

INTERMACS Transplanted 40% Dead 29% Alive 26% Recovery 5% Months after Device Implant Proportion of patients Competing Outcomes – Level 3: Stable but Inotrope Dependent (n=35) Alive Transplanted Dead Months after Device Implant Competing Outcomes – Level 2: Progressive Decline (n=148) Proportion of patients Competing Outcomes – Level 1: Critical Cardiogenic Shock (n=186) Transplanted Alive Dead Months after Device Implant

Evolution of mechanical circulatory support…ventricular assist devices Moratorium of decision Bridge to recovery Bridge to transplant Destination (CMS) Are VADs an operation…or part of an integrated heart failure program? Slaughter M (2010) Will destination therapy be limited to large transplant centers? Texas Heart Inst J 37(5): 562

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

LVAD induced remodeling: Basic science and clinical implications for recovery * biomarkers of recovery (genetic, structural, metabolic) * therapeutic intervention (pre, post, and peri) * etiology of CHF (sequential tissue) May ‘ 08 Inotrope dependent Leftward shift of the EDPVR (structural “reverse remodeling”) Dec ‘ 08 Time dependent reduction in heart size (EDP of 30 mm. Hg, V 30) Dec ‘ 08 Regression of cellular hypertrophy LVAD BNP Preexplant(12) inotropes LVAD pod 1 Explant pod 1 Feb ‘ 09 s/p LVAD Explant pod 7(103)

LVAD induced remodeling: Basic science and clinical implications for recovery May ‘ 08 Inotrope dependent Leftward shift of the EDPVR (structural “reverse remodeling”) Dec ‘ 08 LVAD Feb ‘ 09 s/p LVAD Time dependent reduction in heart size (EDP of 30 mm. Hg, V 30) Regression of cellular hypertrophy