Novel Devices for End-Stage Heart Failure

Transcription

1 Novel Devices for End-Stage Heart Failure Lynne Warner Stevenson No conflicts of interest Off-label assist devices and expanded indications will be discussed

2 Devices for End-Stage Heart Failure New definitions for End-Stage heart failure not just Class IV any more New success and adverse events with devices in evolution Half-hearted solution? New decisions for end-stage heart failure

3 + Therapy to decrease risk In asymptomatic patients ACC/AHA Stages: One-way progression A Risk B Asx Structural dx C Sx ever D= IV Sx Refractory to Optimal Med Rx NYHA 1 timepoint Back and forth NYHA I II III Fine Almost fine Relieve symptoms NYHA IV Anticipate death soon

4 Our Therapies Drive the Definitions of Patients ACC/AHA Stages: One-way progression A Risk B Asx Structural dx C Sx ever 1 point in time NYHA Symptom Class: Back and forth NYHA I II III D= IV sx Refractory to Optimal Med Rx NYHA IV INTERMACS Profiles Therapies to treat end-stage heart failure Profiles integrate severity and tempo

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6 PROFILE-LEVEL INTERMACS LEVEL 1 INTERMACS LEVEL 2 PRIMARY LVADs Official Shorthand Curr FDA Indic Modifier options 24% Crash and burn + Arrhythmias 43% Sliding fast on ino + Arrhythmias INTERMACS LEVEL 3 17% Stable but Ino-Dependent Can be hosp or home + Arrhythmias + FF frequent flyer INTERMACS LEVEL 4 10% Resting symptoms on oral therapy at home. +FF frequent flyer + Arrhythmias INTERMACS LEVEL 5 INTERMACS LEVEL 6 2.5% Housebound, Comfortable at rest, symptoms with minimum activity ADL 1.4% Walking wounded -ADL possible but meaningful activity limited +FF frequent flyer + Arrhythmias +FF frequent flyer + Arrhythmias A INTERMACS LEVEL 7 0 Advanced Class III + Arrhythmias

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8 Slow Increase in Proportion of Ambulatory Patients Receiving LVADs % Pts 35 Receiving 30 Approved Durable 25 LVADs Crash And Burn Inotropes INTERMACS PROFILES Year 1 Year Home Ambulatory IV On Oral Rx Marissa Miller et al, Circ 2010

9 Devices for End-Stage Heart Failure New definitions for End-Stage heart failure not just Class IV any more New success and adverse events with devices in evolution Half-hearted solution? New decisions for advanced heart failure

10 % Survival INTERMACS: Jun 23, 2006 Mar 30, 2007 Prospective Patients: n=156 Months % Survival 1 87% 3 75% 6 75% Event: Death EARLY RESULTS Month Survival 75% n=156, deaths=32 Months after Device Implant

11 Outcomes By Device Outcomes By Intent of Support LV Assist LV Assist LV Assist BiVAD Total Heart Pulsatile Continuous flow rotary Continuous centrifugal Combinations Intrapericardial Different Plans And Different Patients Bridge to Transplant Yes Yes (X) X + X Destination Lifetime Support Yes Yes REVIVE-IT Trial to start in less sick

12 The Destination is Beyond the Bridge XVE Novacor HMII Heartware Pulsatile Pulsatile Continuous Flow Continuous flow BRIDGE All Nonrandomized Outcome Median support pts 48 historical control Frazier JTCVS No control Portner No control Miller days 91 days 126 days 3-6 month 68% 68% 75% Heartware vs Contemporary Control from INTERMACS Endpt Transplant or 180 Day Survival 92% vs 90.1% DESTINATION Controlled REMATCH Randomized Vs. Optimal Med Rx INTREPID LVAD vs LVAD Declined Randomized HMII Device Vs. XVE Device Outcome XVE LVAD HMII device Survival > Med > inotropes > XVE device But 1/3 devices failed but poor survival 1 year 58 vs 23% Med 27 vs 11% 68 vs 55% 2 year 25 vs 8% Med 58 vs 24% Rose 2001 Rogers 2007

13 Continuous Flow Centrifugal, Intrapericardial Pump

14 Early Data Shows Comparable Survival on Centrifugal Pump vs Rotary Pump Centrifugal 26/140 Rotary 127/499 Limited 1-Year Data From Bridge Trials Aaronson et al for ADVANCE Trial AHA 2010

15 PROFILE-LEVEL INTERMACS LEVEL 1 INTERMACS LEVEL 2 APPROVED DEVICE 8 52% Official Shorthand NEW DEVICE Crash and burn 5 Sliding fast on ino 28% INTERMACS LEVEL 3 21% Stable but Ino-Dependent Can be hosp or home 44% INTERMACS LEVEL 4 20% Resting symptoms on oral therapy at home. 23% MORE LESS SICK PROFILES SICK PROFILES

16 The Destination is Beyond the Bridge XVE Novacor HMII Heartware Pulsatile Pulsatile Continuous Flow Continuous flow BRIDGE All Nonrandomized Outcome Median support pts 48 historical control Frazier JTCVS No control Portner No control Miller days 91 days 126 days 3-6 month 68% 68% 75% DESTINATION Controlled Outcome Survival REMATCH Randomized Vs. Optimal Med Rx XVE > Med But 1/3 devices failed INTREPID LVAD vs LVAD Declined LVAD > inotropes but poor survival Randomized HMII Device Vs. XVE Device HMII device > XVE device 1 year 58 vs 23% Med 27 vs 11% 68 vs 55% 2 year 25 vs 8% Med 58 vs 24% Rose 2001 Rogers 2007 Heartware vs Contemporary Control from INTERMACS Endpt Transplant or 180 Day Survival 92% vs 90.1% To Begin: REVIVE-IT Randomized Trial vs Medical Rx For Less Sick Ambulatory Population INTERMACS 4-6

17 Outcomes By Device Outcomes By Intent of Support LV Assist LV Assist LV Assist BiVAD Total Heart Pulsatile Continuous flow rotary Continuous centrifugal Combinations Intrapericardial Different Plans And Different Patients Bridge to Transplant Yes Yes (X) X + X Long Bridge to Decision Destination Lifetime Support Yes Yes REVIVE-IT Trial to start in less sick

18 Candidates for Transplant (Bridge) Differ from Patients For Lifetime Support (Destination) Trial Population Bridge to Transplant- Miller JM 2007 Device as Destination Slaughter 2009 Age % CAD 37% 66% LVEF Albumin SCreat Hct IV inotropes 89% 77% IABP 41% 23%

19 % Survival June 2006 September 2010: Destination Therapy Adult Primary LVADs: n=2433 P (overall) <.0001 P (BTC vs BTT) =.0002 P (DT vs BTT) < Months after Implant By Device Strategy Groups (at time of implant) BTT listed, n=1016, deaths=120 BTC, n=1028, deaths=198 DT, n=389, deaths=94 Event: Death (censored at transplant or explant due to recovery)

20 All Survival Better With Continuous Flow But Still Better in the Transplant-Listed Teuteberg, Stewart, Jessup et al ISHLT Sessions 2010

21 % Survival June 2006 December 2010: Destination Therapy Adult Primary Continuous Flow LVADs: n=2410 BTT listed, N=997, deaths=108 DT, n=443, deaths=63 P (overall) =.001 P (BTC vs BTT) =.002 P (DT vs BTT) =.002 P (DT vs BTC) = Months after Implant By Device Strategy Groups (at time of implant) BTC, n=990, deaths=165 Event: Death (censored at transplant or explant due to recovery)

22 Change in Devices and Intent for Devices Stewart and Stevenson, 2011; 123:

23 Adverse Event Rates With Continuous Flow Device Bridge-Tx Destination Right heart Failure 17% 23% Per pt-yr Per pt-yr % Patients Vent Arr % Perc lead infx % Sepsis % Stroke % Other Neuro % Psych % Pump replace %

24 Consequences of Loss of Pulsatility: GI Bleeding GI Bleeding Acquired vw Syndrome Events/100 Patient-Years PFP CFP Factor Levels During VAD After Tx VWF Ag Ristocetin Crow et al., JTCVS 2009;137:208 Uriel et al., JACC 2010;56:1207

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26 Complications And Intent of Current Devices Infections Driveline Systemic Stroke Embolic Hemorrhagic Can lead to earlier transplant as Bridge in candidates X Can Rule out Transplant X XX Can limit Length or quality of Destination support XX X XX Bleeding X (x) X Right heart failure Vent Arrhythmias X X XX Aortic Insuff X X X

27 Quality of Life and Functional Capacity With Continuous Flow Device - 79 Patients at 3 Months KCCQ EQ-5D VAS 6 Min Walk Clinical Summary Overall Summary Better QoL / Best Health Status Δ = +77% Δ = +106% Δ = +106% Δ = +91% Worst QoL/ Health Status All paired differences p<0.001 n = 79 Aaronson et al for ADVANCE Investigators AHA

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29 Devices for End-Stage Heart Failure New definitions for End-Stage heart failure not just Class IV any more New success and adverse events with devices in evolution Half-hearted solution? New decisions for end-stage heart failure

30 RV Dysfunction Tipping Point and Paradox Pts with preserved right heart function often have reasonable clinical status on medical therapy despite very low LVEF. RV failure heralds worse symptoms, poor response to medical therapy, to VT ablation, to CRT. Increases inflammation Compromises liver and kidney and nutrition. RV failure cannot be addressed by LVAD alone. Outcomes of bivad are poor.

31 % Survival Implant Dates: June 23, 2006 June 30, 2010 Device Type TAH n = 75, deaths=15 RVAD n=38, deaths=15 LVAD n=2377, deaths=446 ONLY LV SUPPORTED Bi-VAD n=306, deaths=109 p (overall) <.0001 Event: Death (censored at transplant or recovery) Months after Device Implant

32 Total Artificial Heart- 950 Implanted

33 The Total Artificial Heart Old and New Driver

34 % Survival Implant Dates: June 23, 2006 June 30, 2010 Device Type TAH n = 75, deaths=15 RVAD n=38, deaths=15 LVAD n=2377, deaths=446 Bi-VAD n=306, deaths=109 p (overall) <.0001 Event: Death (censored at transplant or recovery) Months after Device Implant

35 RV Failure Where To Go? RV failure is to VADs as pulmonary hypertension was to heart transplantation. How do you measure it? How do you demonstrate reversibility? When is it almost to the point of no return?

36 Devices for End-Stage Heart Failure New definitions for End-Stage heart failure not just Class IV any more New success and adverse events with devices in evolution Half-hearted solution? New decisions for end-stage heart failure

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38 PROFILE-LEVEL INTERMACS LEVEL 1 INTERMACS LEVEL 2 PRIMARY LVADs Official Shorthand Curr FDA Indic Modifier options 24% Crash and burn + Arrhythmias 43% Sliding fast on ino + Arrhythmias INTERMACS LEVEL 3 17% Stable but Ino-Dependent Can be hosp or home + Arrhythmias + FF frequent flyer INTERMACS LEVEL 4 10% Resting symptoms on oral therapy at home. +FF frequent flyer + Arrhythmias INTERMACS LEVEL 5 INTERMACS LEVEL 6 2.5% Housebound, Comfortable at rest, symptoms with minimum activity ADL 1.4% Walking wounded -ADL possible but meaningful activity limited +FF frequent flyer + Arrhythmias +FF frequent flyer + Arrhythmias A INTERMACS LEVEL 7 0 Advanced Class III + Arrhythmias

39 State of the Art MCS 2001 Heart House If you were otherwise in your current age and state of health, but b had, would you want an LVAD? Cardiogenic shock Dependence on IV inotropes Chronic HF on oral therapy, limited to less than 1 block 95% yes 71% yes 81% NO

40 State of the Art MCS June 2011 Gordon Conference - Waterville If you were otherwise in your current age and state of health, but b had, would you want an LVAD? Cardiogenic shock Dependence on IV inotropes Chronic HF on oral therapy, limited to less than 1 block 95% yes 71% yes 81% NO 79% Yes 76% Yes 70% Yes or probably

41 Patients Answer: What Information Would Be Most Important In Choosing to have a VAD? NYHA Class I/II NYHA Class III/IV Surival More Important Survival Equal to Quality Quality More Important Stewart et al, JHLT 2009

42 Techno Highway The Lonely Road? Slide courtesy of Carol Flavell, Senior HF NP

43 1.2 Freedom From Readmission 1.1 Cumulative Proportion Free of Re-Admission Years 1 Year 1.5 Years 2 Years 2.5 Years 3 Years T ime (Years)

44 Comparing Risks: What Do We Think Our Patients Want? What Do We Want For Ourselves? SURVIVAL CHANCE VERSUS STROKE RISK Antaki J, survey Gordon Conference 2011 % What risk of stroke over 2 years would make you decline an LVAD that offered longer life? To increase survival from 50 to 80% To decrease mortality from 50% to 20%

45 The Death of Washington Howard Pyle, Sketch in Oil

46 Death Will Not Be Easy With A VAD

47 79% (54/68) of Current LVAD Centers have a Palliative Care Program LVAD hospital with PC program LVAD hospital without PC program Slide courtesy Of Diane Meier

48 Devices for End-Stage Heart Failure New definitions for End-Stage heart failure not just Class IV any more New success and adverse events with devices in evolution Half-hearted solution? New decisions for advanced heart failure

49 His life is happiest who can embrace change. Albert Schweitzer

50 BiVAD

51 Estimated Direct and Indirect Costs of HF Hospitalization $ % in US 14% Total Cost $39.2 billion Nursing Home $4.7 8% Lost Productivity/ Mortality* $4.1 Home Healthcare $3.8 7% 8% 10% Drugs/Other Medical Durables $3.2 Physicians/Other Professionals $2.5 American Heart Association. Heart Disease and Stroke Statistics. American Heart Association

52 Cost Is Not A Consideration in the U.S.

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54 How To Spend Heart Failure Dollars On Implantable Devices In U.S.? Billions Of Dollars Guaranteed impact: A consistent delay at Airport Security (cost priceless) Current Transplant ICD VAD Assuming increase From 2,000 To 60,000 VAD/yr without improved efficiency Current Projected

55 A Look Ahead To Status 1 Only: Decreasing Relevance of Status 2 And 1B For Transplant In Region 1 90 % of Hearts Going To Status Status 1A Status 1B Status UNOS National Data

56 Watch For It Changing Eras of Patients Evaluated for Transplant s After 2000 R-L Mismatch increased from 1 in 5 to 1 in 4; Doubled proportion of High Right Mismatch. Total Mismatch High Left High Right Campbell, Drazner et al, HFSA 2009 N=1000 N=538

57 Patients Answer: What Information Would Be Most Important In Choosing to have a VAD? 80 NYHA Class I/II NYHA Class III/IV Surival More Important Survival Equal to Quality Quality More Important Stewart et al, JHLT 2009

58 PROFILE-LEVEL INTERMACS LEVEL 1 INTERMACS LEVEL 2 PRIMARY LVADs Official Shorthand Curr FDA Indic Modifier options 24% Crash and burn + Arrhythmias 43% Sliding fast on ino + Arrhythmias INTERMACS LEVEL 3 17% Stable but Ino-Dependent Can be hosp or home + Arrhythmias + FF frequent flyer INTERMACS LEVEL 4 10% Resting symptoms on oral therapy at home. +FF frequent flyer + Arrhythmias INTERMACS LEVEL 5 INTERMACS LEVEL 6 2.5% Housebound, Comfortable at rest, symptoms with minimum activity ADL 1.4% Walking wounded -ADL possible but meaningful activity limited +FF frequent flyer + Arrhythmias +FF frequent flyer + Arrhythmias A INTERMACS LEVEL 7 0 Advanced Class III + Arrhythmias

59 % Survival INTERMACS Level at Implant : June 2006 March 2009 Level 1 (Critical Cardiogenic Shock), n=328, deaths=68 Level 3 (Stable but Inotrope Dependent), n=168, deaths=18 Level 2 (Progressive Decline), n=437, deaths=81 Levels 4,5,6,7: All Others, p (overall) =.01 n=159, deaths=24 Event: Death (censored at transplant or explant recovery) Months after Device Implant LVAD, left ventricular assist device; Primary LVAD: n=1092 Fig 3 EARLY IMPACT OF PATIENT PROFILES ON OUTCOME