Dan M. Meyer, MD 2011 Donald and Lois Roon Visiting Lectureship Wednesday, Sept. 28, 2011
William Pierce, MD What ever happened to the artificial heart? MechanicalMechanical supportsupport ofof thethe failingfailing heart:heart: WillWill heartheart transplantationtransplantation becomebecome obsolete?obsolete?
Dan M. Meyer, MD The 20thth 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 Heart Transplantation History History
Lower + Shumway James Hardy Stanford Univ USA, 1918-2003 First long term successful heart transplant (4th) Univ Mississippi Surg Forum 11:18 1960 1964 First Human 5 dogs survived 6-21 d Orthotopic HTx N=97 HTx 1968-1975 Xenograft (Chimp) Surv-1 yr = 49% 1968 Surv-1 = 22% JAMA 188:1132-40, 1974 Surv-1 = 62% 1964 Surv-5 yr = 23% Dan M. Meyer, MD 2011 Donald and Lois Roon Visiting Lectureship Wednesday, Sept. 28, 2011
Heart Transplantation Life Magazine – Dec. 15, 1967 History
1968 102 heart transplants worldwide 17 countries 52 medical centers median survival = 29 days 1969 Fewer than 50 heart transplants 1970-1975 Fewer than 20 heart transplants per year Stanford (Shumway) Medical College of Virginia (Lower)
Life Magazine - Sept. 17, 1971
HeartMate IP LVAD Dan M. Meyer, MD 2011 Donald and Lois Roon Visiting Lectureship Wednesday, Sept. 28, 2011
LVADs as Destination Therapy REMATCH Update
1.00 1 year LVAD vs. 0.90 VE LVAS (n=71) OMM survival = 0.80 OMM (n=61) 0.70 P=0.0012 53.5% vs. 26.5% 0.60 2 year LVAD vs. 0.50 P=0.0004 0.40 OMM survival = 0.30 P=0.0063 32% vs. 8.2% 0.20 0.10 3 year LVAD vs. 0.00 0 6 12 18 24 30 36 42 48 54 OMM survival = Months Post Enrollment 15.9% vs. 2% (NS)
REMATCH Update (as of April 2004) – Source Thoratec Registry
Improving Outcomes BEYOND REMATCH The Problem
100 Half-life =9.1 years HTx Conditional Half-life = 11.6 years The number of patients with end-stage CHF 80 Actuarial Survival (1982-2000) increasing (Stage D), ~500,000 in the US LVAD 60 “ IMPROVEMENTS with: LDSH ~ 10% of patients >65yo LV dysfunction - DEVICES N=52,195 40 - MANAGEMENT LVAD This number is expected to double in 25 yrs
Survival (%) Survival LESS ADVANCED Illness 20 (Patient Selection) The number of available donors are not OMM expected to increase, numbering 2200 in US 0 01234567891011121314151617 Years Post-Transplantation
Heart Failure Expected to Become More Treatment Options Common as Population Ages Common as Population Ages End-Stage Heart Failure
Medical management - limited by poor outcomes
Cardiac transplantation - limited by donor shortage
Mechanical circulatory support devices Left ventricular assist device (LVAD) Heart Failure‐Epidemiology Forecasts to 2015. Datamonitor 2002 Dan M. Meyer, MD 2011 Donald and Lois Roon Visiting Lectureship Wednesday, Sept. 28, 2011
Congestive Heart Failure HEART TRANSPLANTATION Medical Rx Survival Kaplan-Meier Survival (1/1982-6/2008)
100 Half-life = 10.0 years Conditional Half-life = 13.0 years 80
60 HEARTN=80,038 TRANSPLANTATION
Kaplan-Meier40 Survival (1/1982-6/2005) N at risk at 23 years = 124 Survival (%) (%) Survival
20
0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 Years
ISHLT 2010 Gorodeski et al. Circ Heart Fail 2009;2:320-324 J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141
Loss of Pulsatility with Increased RPM Thoratec HeartMate II LVAD Pump
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 2011 23 25 JAAC 2009;54(4):312-21. Dan M. Meyer, MD 2011 Donald and Lois Roon Visiting Lectureship Wednesday, Sept. 28, 2011
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, 2009.
ADVANCE Trial Secondary Outcome: Survival Indications for LVAD Placement 100 Bridge to Decision HVA Bridge to Transplant 90 D Destination Therapy Control Bridge to Recovery 80 Days Post Treatment Control Implant p = .39 30 98.6% 96.6% % Survival % 90 95.6% 93.6% 70 Event: Death (censored at 180 93.9% 90.2% transplant or recovery)
360 90.6% 85.7% ITT Population
60 0 60 120 180 240 300 360 Days Post Implant
Patients Treatment 140 128 108 92 63 36 26 at Risk Control 499 440 370 305 228 176 127
Patient Selection/Stabilization Timing of LVAD is Key to Survival
Too Late
Futile Implants 1-Year Survival Operative 19% Risk Death Successful 1-Year Survival Implants 69%
Worsening nutritional, end-organ, and RV function
Lietz et al. Circulation. 2007;116(5):497 Dan M. Meyer, MD 2011 Donald and Lois Roon Visiting Lectureship Wednesday, Sept. 28, 2011
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 National Shift in Timing of Implants INTERMACS Profile
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 and ventricular arrythmias LVAD and renal recovery LVAD and gastrointestinal bleeding Dan M. Meyer, MD 2011 Donald and Lois Roon Visiting Lectureship Wednesday, Sept. 28, 2011
Study Protocol Study Protocol Phase 1 Phase 2 Instrumentation ECG/HR BP Instrumentation cuff (Korotkoff /Doppler) ECG/HR beat-by-beat finger arterial BP (Nexfin) BP cuff (Korotkoff /Doppler) TCD recording from a non-pulsatile LVAD beat-by-beat finger arterial BP (Nexfin) patient Microneurography (MSNA) Sympathetic multiunit activity occurs as “bursts” peroneal nerve Transcranial Doppler (TCD) burst recordings Sitting/Standing Maneuvers – 0.05 Hz Head up tilting supine, 30°, and 60° Transfer function estimation – cross spectral method of gain, phase, Cardiac output and coherence acetylene rebreathing technique 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
130 120 110 HR 100 HR 90 80 70 Nitroprusside Phenylephrine 30 s 120 110 100 90 80
BP (mmHg) BP 70 60 50
0.2
0.0
-0.2
MSNA -0.4
-0.6
-0.8
Conclusions Clinical Implications
Non-pulsatile LVAD patients have dramatically higher sympathetic activity than pulsatile patients and controls, Higher sympathetic activity could lead to adverse presumably due to greater baroreceptor unloading (impaired baroreceptor function) events in these patients over time: CV events, stroke, high blood pressure, renal effects Cerebral autoregulation does not seem to be significantly affected in nonpulsatile devices, at least at It may be possible to develop surrogate measures of the frequency of normal activity sympathetic activity to guide therapy in these Variability in CBFV and BP during sit-stand is relatively low in nonpulsatile devices compared to pulsatile patients There may need to be some “built in” pulsatility in More data and larger studies are needed to further define devices that are primarily non-pulsatile: the physiology of nonpulsatility with change in speed, devices that are primarily non-pulsatile: position, exercise, and device optimization How to do that? What frequency? What duration? Dan M. Meyer, MD 2011 Donald and Lois Roon Visiting Lectureship Wednesday, Sept. 28, 2011
Nexfin - Blood pressure measurement Nexfin integrative hemodynamics
One screen:
Blood pressure + Cardiac Output Brachial pressure + Hemodynamics + ECG
Touch screen user interface
Finger pressure Brachial pressure
9/28/2011 43 9/28/2011 44
A Study of Blood Pressure Measurement in Patients Increased LVAD Utilization with Non-pulsatile Left Ventricular Assist Devices
Findings: In the first 10 subjects, correlation of BMEYE with A-line measurements is stronger than Doppler with A-line measurements.
Doppler and A- BMEYE and A- line line Pearson’s 0.8 0.9 coefficient
Interclass 0.861 0.911 correlation
LVAD Program Growth Dan M. Meyer, MD 2011 Donald and Lois Roon Visiting Lectureship Wednesday, Sept. 28, 2011
Quality Program Details Intermacs Quality Assurance Report Performance Measures Adverse Events
Baylor University Medical Center INTERMACS Adverse Events #%#% Bleeding 104 23 4317 17.5 Cardiac Arrhythmia 15 3.3 1591 6.4 Death 14 3.1 747 3 Device Malfunction 37 8.2 712 2.8
NeurologicInfection 30 6.6 3472 14 Dysfunction 14 3.1 687 2.7 Psychiatric Episode 24 5.9 396 1.6 Rehospitalization 81 17.9 4774 19.3 July 2011
CMS Eligibility Criteria DT Gaining Popularity Destination Therapy
Class III-IV CHF EF < 25% Significant functional limitations despite OMM for at least 60 days
VO2max < 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;123:1559-68.
Destination Therapy Centers Destination Therapy Dan M. Meyer, MD 2011 Donald and Lois Roon Visiting Lectureship Wednesday, Sept. 28, 2011
Heartmate II in patients > 70 years of age Heartmate II in patients > 70 years of age
J Am Coll Cardiol 2011;57:2487-95 J Am Coll Cardiol 2011;57:2487-95
HeartMate II LVADs as Destination Therapy Improvement in DT Outcomes Patient Management It’s a collaborative effort The total heart treatment team includes: Referring physician Heart failure cardiologist VAD NP/coordinator Cardiovascular surgeon Other implanting center team members/social services, financial, psychiatry, nutritionist, rehabilitation services Patient and family
Slaughter MS, Rogers JG, Milano CA, et al. Advanced heart failure treated with continuous-flow left ventricular assist device. N Engl J Med. 2009;361:2241-51. Community Park SJ. AHA Scientific Sessions, November 2010.
LVAD DT vs Extended Criteria LVAD DT vs Extended Criteria Cardiac Transplant Cardiac Transplant
Ann Thorac Surg2010;89:1205-10 Ann Thorac Surg 2010;89:1205-10 Dan M. Meyer, MD 2011 Donald and Lois Roon Visiting Lectureship Wednesday, Sept. 28, 2011
Heart transplant vs LVAD in heart Heart transplant vs LVAD in heart transplant –eligible patients transplant –eligible patients
Williams et al. Ann Thorac Surg 2011;91:1330-4 Williams et al. Ann Thorac Surg 2011;91:1330-4
Heart transplant vs LVAD in heart 2011 Hospital Medicare Inpatient transplant –eligible patients Reimbursement
DRG-1 Payment Over Time
Williams et al. Ann Thorac Surg 2011;91:1330-4
Myocardial recovery with continuous Myocardial recovery with continuous flow pumps flow pumps
Birks et al. Circulation.2011;123:381-390 Birks et al. Circulation.2011;123:381-390 Dan M. Meyer, MD 2011 Donald and Lois Roon Visiting Lectureship Wednesday, Sept. 28, 2011
Felt plug with video
Conclusions Quality of Life Landscape of chronic HF has changed due to emerging advanced therapies
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 Dan M. Meyer, MD 2011 Donald and Lois Roon Visiting Lectureship Wednesday, Sept. 28, 2011
INTERMACS Profiles Patient Selection Level Key feature of level Descriptive label CMS Patient Selection Criteria for Bridge to Transplantation: 1 Critical cardiogenic shock “Crash and burn” A. Patient approved/listed for heart transplantation B. Implanting site needs written permission from patient’s 2 Progressive decline Inotropes, slipping transplant center CMS Patient Selection Criteria for Destination Therapy: 3 Stable but inotrope dependent Inotropes, stable NYHA Class IV ≥ 90 days & life expectancy < 2 yrs: 4 Recurrent decompensations “Frequent flyer” A. Not heart transplant candidate 5 Exertion intolerant Housebound B. NYHA Class IV heart failure symptoms failed to respond to OMT 6 Exertion limited “Walking wounded” for at least 60 of the last 90 days (fatigue within minutes) C. LVEF < 25% 7 NYHA IIIA Too well for D. Peak oxygen consumption of < 12 ml/kg/min or continued need VAD/Transplant for IV inotropes E. BSA ≥ 1.5 m² if a first generation VAD is used Stevenson L, et al JACC, 2007 CMS National Coverage Determination 2007
Indications for LVAD Placement Charles Lindbergh • Bridge to Tranplant • Destination Therapy • Bridge to Candidacy • Bridge to Recovery Dan M. Meyer, MD 2011 Donald and Lois Roon Visiting Lectureship Wednesday, Sept. 28, 2011
Making an impact….. Sample Individual MSNA Recordings During HUT
Pulsat Non- ile Pulsatile
Supine
30 HUT
60 HUT
10 sec 10 sec
Timeframe for Definitive Interventions based on INTERMACS classifications
AHA/ACC Stage C Stage D classification
NYHA Class III Class IIIb/IV Class IV classifications
INTERMACS levels 7 6 5 4 3 2 1
Brief Advanced Exertion Exercise Recurrent Stable but Progressive Critical descriptions NYHA Class limited/ intolerant/ decompen- inotrope- decline/ cardiogenic III “Walking “House- sation/ dependent/ “Sliding on shock/ “Crash wounded” bound” “Frequent “Dependent inotropes” and burn” flyer” stability” Timeframe for Transplan- Variable, Variable, Elective over Elective over a Needed within Needed within definitive tation or depends upon depends upon weeks to few weeks a few days hours intervention circulatory nutrition, organ nutrition, organ months as long support not function, and function, and as treatment of currently activity activity episodes indicated restores stable baseline, including nutrition
Sources: “Heart Failure”. NEJM 2003; 348:2007-18. “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; 155:341-9. INTERMACS Manual of Operations version 2.2, User’s Guide
Natural History of Heart Failure
Class III
100 10 25% of HF Patients
Frequent 75 hospitalizations
year
Worsening symptoms / despite drug therapy Rate
50 1 Significant opportunity for new therapies Survival 25 Survival Rate Hospitalizations Hospitalizations
Annual .1 0 I II III IV Deceased NYHA CLASS
Adapted from Bristow, MR Management of Heart Failure, Heart Disease: A Textbook of Cardiovascular Medicine, 6th edition, ed. Braunwald et al. Dan M. Meyer, MD 2011 Donald and Lois Roon Visiting Lectureship Wednesday, Sept. 28, 2011
System Components HeartMate II LVAS Pump
. HM II Components: . Flexible inflow conduit Implantable titanium blood . Textured surfaces pump Inlet cannula, inflow and System Controller outflow elbows Thrombo-resistant . Shared Components: . Outflow graft with bend System Monitor relief . Display Module . Anastomosed to LV apex and ascending aorta Power Sources . Pump output varies over Power Base Unit cardiac cycle Batteries & Clips Follows native pulse Emergency Power Pack Afterload sensitive Accessories
Lower INTERMACS Score Associated With Decreased Survival
HR 2.7 (1.1–7) P < 0.005 80% N = 54 72% 62% INTERMACS 3-4 54% 41% 27% INTERMACS 1-
Alba AC. J Heart Lung Transplant 2009; 28:827-33. Dan M. Meyer, MD 2011 Donald and Lois Roon Visiting Lectureship Wednesday, Sept. 28, 2011
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 measurement Methods: Measurements are made with a non-invasive finger beat-to- beat plethysmography (BMEYE device), a Doppler ultrasound machine, and an arterial line in the post-op ICU setting. Measurements are made in the below three scenarios to validate the 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.