Mechanical support of the failing heart: Will heart transplantation become obsolete? Charles Lindbergh

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1 William Pierce, MD What ever happened to the artificial heart? Mechanical support of the failing heart: Will heart transplantation become obsolete? Dan M. Meyer, MD The 20 th Annual Donald and Lois Roon Visiting Lectureship Scripps Green Hospital September 28, 2011 Jack Copeland, MD Surgical treatment of advanced heart disease Charles Lindbergh Heart Transplantation History Lower + Shumway Stanford Univ First long term successful heart transplant (4 th ) Surg Forum 11: dogs survived d N=97 HTx Surv-1 1 yr = 49% 1968 Surv-1 1 = 22% 1974 Surv-1 1 = 62% Surv-5 5 yr = 23% Heart Transplantation History James Hardy USA, USA, UnivUniv Mississippi First Human Orthotopic HTx Xenograft (Chimp) JAMA JAMA 188: , 1964

2 Life Magazine Dec. 15, 1967 Heart Transplantation History heart transplants worldwide 17 countries 52 medical centers median survival = 29 days 1969 Fewer than 50 heart transplants Fewer than 20 heart transplants per year Stanford (Shumway( Shumway) Medical College of Virginia (Lower) Life Magazine - Sept. 17, 1971 HeartMate IP LVAD

3 LVADs as Destination Therapy REMATCH Update VE LVAS (n=71) 0.80 OMM (n=61) 0.70 P= P= P= Months Post Enrollment 1 year LVAD vs. OMM survival = 53.5% vs. 26.5% 2 year LVAD vs. OMM survival = 32% vs. 8.2% 3 year LVAD vs. OMM survival = 15.9% vs. 2% (NS) REMATCH Update (as of April 2004) Source Thoratec Registry Survival (%) Improving Outcomes BEYOND REMATCH HTx LVAD LDSH LVAD Half-life =9.1 years Conditional Half-life = 11.6 years Actuarial Survival ( ) IMPROVEMENTS with: - DEVICES - MANAGEMENT LESS ADVANCED Illness (Patient Selection) OMM Years Post-Transplantation N=52,195 The Problem The number of patients with end-stage CHF increasing (Stage D), ~500,000 in the US ~ 10% of patients >65yo LV dysfunction This number is expected to double in 25 yrs The number of available donors are not expected to increase, numbering 2200 in US Heart Failure Expected to Become More Common as Population Ages Treatment Options End-Stage Heart Failure Medical management - limited by poor outcomes Cardiac transplantation - limited by donor shortage Heart Failure Epidemiology Forecasts to Datamonitor 2002 Mechanical circulatory support devices Left Left ventricular assist device (LVAD)

4 Congestive Heart Failure Medical Rx Survival HEART TRANSPLANTATION Kaplan-Meier Survival (1/1982-6/2008) Half-life = 10.0 years Conditional Half-life = 13.0 years Survival (%) 60 HEART TRANSPLANTATION Kaplan-Meier Survival (1/1982-6/2005) 40 N=80,038 N at risk at 23 years = Gorodeski et al. Circ Heart Fail 2009;2: Years ISHLT 2010 J Heart Lung Transplant Oct; 29 (10): Thoratec HeartMate II LVAD Pump Loss of Pulsatility with Increased RPM Worldwide Clinical Experience HeartMate II BTT Long-term Results (n=281) More than 8,000 patients worldwide have now been implanted with the HeartMate II LVAS. Patients supported 1 year: 2978 Patients supported 2 years: 1108 Patients supported 3 years: 300 Patients supported 4 years: 136 Patients supported 5 years: 33 Patients supported 6 years: 9 As of Sept JAAC 2009;54(4):

5 Kaplan-Meier Survival (n=281) HeartWare LVAD HVAD miniaturized implantable blood pump Provides up to 10 L/min of flow Centrifugal design, continuous flow Hybrid magnetic / hydrodynamic impeller suspension Optimizes flow, pump surface washing, and hemocompatibility Pagani F, Miller L, Russell S, JAAC: Vol 54, No 4, ADVANCE Trial Secondary Outcome: Survival % Survival Days Post Implant Treatment Control % 96.6% % 93.6% % 90.2% % 85.7% HVA D Control p =.39 Event: Death (censored at transplant or recovery) ITT Population Indications for LVAD Placement Bridge to Decision Bridge to Transplant Destination Therapy Bridge to Recovery Patients at Risk Days Post Implant Treatment Control Patient Selection/Stabilization Timing of LVAD is Key to Survival Operative Risk Death Futile Implants Successful Implants Too Late 1-Year Survival 19% 1-Year Survival 69% Worsening nutritional, end-organ, and RV function Lietz et al. Circulation. 2007;116(5):497

6 INTERMACS Profiles Level Key feature of level Descriptive label 1 Critical cardiogenic shock Crash and burn 2 Progressive decline Inotropes, slipping 3 Stable but inotropic dependent Inotropes, stable 4 Recurrent decompensations Frequent flyer 5 Exertion intolerant Housebound 6 Exertion limited Walking wounded (fatigue within minutes) 7 NYHA IIIA Too well for VAD/Transplant Stevenson L, et al JACC, 2007 Clinical Outcomes INTERMACS Profile National Shift in Timing of Implants Length of Stay Post-VAD Actuarial Survival Post-VAD Less acutely ill, ambulatory patients in INTERMACS profiles 4 7 had better survival and reduced length of stay compared to patients who were more accurately ill in profiles 1 3. Group 1: INTERMACS 1 Group 2: INTERMACS 2 3 Group 3: INTERMACS 4 7 Boyle, Ascheim, Russo, et al. JHLT. 2011;30:4. Current research efforts Assessment of sympathetic nerve activity in non-pulsatile systems Non-invasive monitoring of the LVAD patient Clinical studies LVAD LVAD and ventricular arrythmias LVAD LVAD and renal recovery LVAD LVAD and gastrointestinal bleeding

7 Phase 1 Instrumentation ECG/HR BP cuff (Korotkoff /Doppler) beat-by-beat finger arterial BP (Nexfin) Microneurography (MSNA) peroneal nerve burst recordings Head up tilting supine, 30, and 60 Cardiac output acetylene rebreathing technique Study Protocol Sympathetic multiunit activity occurs as bursts Phase 2 Instrumentation ECG/HR BP cuff (Korotkoff /Doppler) beat-by-beat finger arterial BP (Nexfin) Transcranial Doppler (TCD) Sitting/Standing Maneuvers 0.05 Hz Transfer function estimation cross spectral method of gain, phase, and coherence Study Protocol TCD recording from a non-pulsatile LVAD patient TCD recording from a pulsatile LVAD patient An LVAD patient undergoing head up tilting Total study time: approximately 6-7 hours involving about Total study time is approximately 6-7 hours involving about 15 investigators Sympathetic and Cardiovascular Responses During Bolus Injection of Nitroprusside and Phenylephrine in a Nonpulsatile Patient HR HR Nitroprusside Phenylephrine 30 s 110 BP (mmhg) MSNA Conclusions Non-pulsatile LVAD patients have dramatically higher sympathetic activity than pulsatile patients and controls, presumably due to greater baroreceptor unloading (impaired baroreceptor function) Cerebral autoregulation does not seem to be significantly affected in nonpulsatile devices, at least at the frequency of normal activity Variability in CBFV and BP during sit-stand stand is relatively low in nonpulsatile devices compared to pulsatile More data and larger studies are needed to further define the physiology of nonpulsatility with change in speed, position, exercise, and device optimization Clinical Implications Higher sympathetic activity could lead to adverse events in these patients over time: CV events, stroke, high blood pressure, renal effects It may be possible to develop surrogate measures of sympathetic activity to guide therapy in these patients There may need to be some built in pulsatility in devices that are primarily non-pulsatile pulsatile: How to do that? What frequency? What duration?

8 Nexfin - Blood pressure measurement Nexfin integrative hemodynamics One screen: Brachial pressure Blood pressure + Cardiac Output + Hemodynamics + ECG Touch screen user interface Finger pressure Brachial pressure 9/28/ /28/ A Study of Blood Pressure Measurement in Patients with Non-pulsatile Left Ventricular Assist Devices Increased LVAD Utilization Findings: : In the first 10 subjects, correlation of BMEYE with A-line A measurements is stronger than Doppler with A-line A measurements. Pearson s coefficient Interclass correlation Doppler and A- line BMEYE and A- line LVAD Program Growth

9 Quality Program Details Performance Measures Intermacs Quality Assurance Report Adverse Events Baylor University Medical Center INTERMACS Adverse Events # % # % Bleeding Cardiac Arrhythmia Death Device Malfunction Infection Neurologic Dysfunction Psychiatric Episode Rehospitalization July 2011 CMS Eligibility Criteria Destination Therapy DT Gaining Popularity Class III-IV IV CHF EF < 25% Significant functional limitations despite OMM for at least 60 days VO 2 max < 12 ml/kg/min or inotrope dependent Inability to tolerate OMM No conditions which limit life expectancy Acceptable surgical risk (nutrition, organ function) Stewart G, et al Circ 2011;123: Destination Therapy Centers Destination Therapy

10 Heartmate II in patients > 70 years of age Heartmate II in patients > 70 years of age J Am Coll Cardiol 2011;57: J Am Coll Cardiol 2011;57: HeartMate II Improvement in DT Outcomes Slaughter MS, Rogers JG, Milano CA, et al. Advanced heart failure treated with continuous-flow left ventricular assist device. N Engl J Med. 2009;361: Park SJ. AHA Scientific Sessions, November LVADs as Destination Therapy Patient Management It s s a collaborative effort The total heart treatment team includes: Referring Referring physician Heart Heart failure cardiologist VAD VAD NP/coordinator Cardiovascular surgeon Other Other implanting center team members/social services, financial, psychiatry, nutritionist, rehabilitation services Patient Patient and family Community LVAD DT vs Extended Criteria Cardiac Transplant LVAD DT vs Extended Criteria Cardiac Transplant Ann Thorac Surg 2010;89: Ann Thorac Surg2010;89:

11 Heart transplant vs LVAD in heart transplant eligible patients Heart transplant vs LVAD in heart transplant eligible patients Williams et al. Ann Thorac Surg 2011;91: Williams et al. Ann Thorac Surg 2011;91: Heart transplant vs LVAD in heart transplant eligible patients 2011 Hospital Medicare Inpatient Reimbursement DRG-1 Payment Over Time Williams et al. Ann Thorac Surg 2011;91: Myocardial recovery with continuous flow pumps Myocardial recovery with continuous flow pumps Birks et al. Circulation.2011;123: Birks et al. Circulation.2011;123:

12 Felt plug with video Conclusions Landscape of chronic HF has changed due to emerging advanced therapies Quality of Life LVAD utilization is gaining increased acceptance as device technology improves Placement of LVADs earlier in the spectrum of advanced heart failure (INTERMACS PROFILES) is associated with better outcomes Efforts to improve DT LVAD outcomes, perhaps not transplantation, represents the greatest hope for addressing end stage heart failure

13 INTERMACS Profiles Level Key feature of level Descriptive label 1 Critical cardiogenic shock Crash and burn 2 Progressive decline Inotropes, slipping 3 Stable but inotrope dependent Inotropes, stable 4 Recurrent decompensations Frequent flyer 5 Exertion intolerant Housebound 6 Exertion limited Walking wounded (fatigue within minutes) 7 NYHA IIIA Too well for VAD/Transplant Stevenson L, et al JACC, 2007 Patient Selection CMS Patient Selection Criteria for Bridge to Transplantation: A. Patient approved/listed for heart transplantation B. Implanting site needs written permission from patient s transplant center CMS Patient Selection Criteria for Destination Therapy: NYHA Class IV 90 days & life expectancy < 2 yrs: A. Not heart transplant candidate B. NYHA Class IV heart failure symptoms failed to respond to OMT for at least 60 of the last 90 days C. LVEF < 25% D. Peak oxygen consumption of < 12 ml/kg/min or continued need for IV inotropes E. BSA 1.5 m² if a first generation VAD is used CMS National Coverage Determination 2007 Charles Lindbergh Indications for LVAD Placement Bridge to Tranplant Destination Therapy Bridge to Candidacy Bridge to Recovery

14 Making an impact.. Sample Individual MSNA Recordings During HUT Pulsat ile Non- Pulsatile Supine 30 HUT 60 HUT 10 sec 10 sec Timeframe for Definitive Interventions based on INTERMACS classifications AHA/ACC classification NYHA classifications Stage C Class III Class IIIb/IV Class IV Stage D INTERMACS levels Brief descriptions Advanced NYHA Class III Exertion limited/ Walking wounded Exercise intolerant/ Housebound Recurrent decompensation/ Frequent flyer Stable but inotropedependent/ Dependent stability Progressive decline/ Sliding on inotropes Critical cardiogenic shock/ Crash and burn Timeframe for definitive intervention Transplantation or circulatory support not currently indicated Variable, Variable, Elective over Elective over a Needed within Needed within depends upon depends upon weeks to few weeks a few days hours nutrition, organ nutrition, organ months as long function, and function, and as treatment of activity activity episodes restores stable baseline, including nutrition Sources: Heart Failure. NEJM 2003; 348: On the Fledgling Field of Mechanical Circulatory Support. JACC 2007; (50) 8. Characteristics of Stage D heart failure: Insights from the Acute Decompensated Heart Failure National Registry Longitudinal Module (ADHERE LM). Am J Heart 2008; 155: INTERMACS Manual of Operations version 2.2, User s Guide Natural History of Heart Failure Class III % of HF Patients Annual Survival Rate I II III IV 1.1 Hospitalizations / year Deceased Frequent hospitalizations Worsening symptoms despite drug therapy Significant opportunity for new therapies Survival Rate Hospitalizations NYHA CLASS Adapted from Bristow, MR Management of Heart Failure, Heart Disease: A Textbook of Cardiovascular Medicine, 6th edition, ed. Braunwald et al.

15 System Components HM II Components: Implantable titanium blood pump System Controller Shared Components: System Monitor Display Module Power Sources Power Base Unit Batteries & Clips Emergency Power Pack Accessories Flexible inflow conduit Textured surfaces Inlet cannula,, inflow and outflow elbows Thrombo-resistant resistant Outflow graft with bend relief Anastomosed to LV apex and ascending aorta Pump output varies over cardiac cycle Follows native pulse Afterload sensitive HeartMate II LVAS Pump Lower INTERMACS Score Associated With Decreased Survival 80% 54% 72% 41% 62% 27% HR 2.7 (1.1 7) P < N = 54 INTERMACS 3-4 INTERMACS 1- Alba AC. J Heart Lung Transplant 2009; 28:

16 A Team Effort A Study of Blood Pressure Measurement in Patients with Non-pulsatile Left Ventricular Assist Devices. Background: The most accurate technique for measuring blood pressure in patients with non-pulsatile assist devices is currently unknown. Goal: Compare various techniques of blood pressure measurement in LVAD patients with the gold standard of an a-line a measurement Methods: Measurements are made with a non-invasive finger beat-to to- beat plethysmography (BMEYE device), a Doppler ultrasound machine, and an arterial line in the post-op op ICU setting. Measurements are made in the below three scenarios to validate the t accuracy of each device when blood pressure is expected to change. 1. Orthostatic blood pressure measurements 2. Before, during and after the subject performs the valsalva maneuver 3. Change in LVAD pump speed higher than baseline and lower than baseline.