New Trends and Indications for LVADs

Transcription

1 New Trends and Indications for LVADs Mark S. Slaughter, MD Professor and Chief Division of Thoracic and Cardiovascular Surgery University of Louisville

2 Natural History of Heart Failure Class III 25% 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.

3 Hall & Debakey VAD

4 LVAD Bridge to Recovery

5 The Evolution of MCS Devices Paracorporeal Implantable Implantable Implantable Implantable Pneumatic Electric Electric Electric Electric Pulsatile Uni- or Biventricular Pulsatile Large Multiple moving parts Continuous flow Axial design Smaller Single moving part Continuous flow Centrifugal design Smaller Bearingless Continuous flow Axial design Smaller Partial support

6 Improving Survival in LVAD Trials Percent Survival HM II BTT Starling HFSA Months HM II BTT Pagani JACC 2009 HM II BTT Miller NEJM 2007 HM II DT Slaughter NEJM 2009 VE DT LVAD REMATCH Rose NEJM 2001 XVE DT LVAD Slaughter NEJM 2009 Novacor DT LVAD INTrEPID Rogers JACC 2007 OMM REMATCH Rose NEJM 2001 OMM INTrEPID Rogers JACC 2007

7 Destination Therapy Trials Fang JC NEJM 2009

8 Percent Survival Two Center Improvement in DT Survival Since First Cohort % % Late Experience June April 2009 (n=55) Overall Experience March April 2009 (n=93) Early experience March May 2007 (n=38) (Included in Slaughter, Rogers, Milano et al NEJM 2009) Remaining at Risk: Months % %

9 Multicenter Improvement in DT Survival HeartMate II Clinical Trial Percent Survival DT Implants mid trial (n=311) ( thru ) % % DT Implants early trial (n=133) ( thru ) (Slaughter, Rogers, Milano NEJM 2009) Months % Remaining at Risk:

10 J Am Coll Cardiol 2010; 55: Patient Functionality and QoL on VAD Therapy NYHA Functional Class 6 Minute Walk Distance Minnesota Living with Heart Failure

11 Bleeding vs. Thromboembolism Which is one is a problem? Does it matter?

12 Bleeding vs. Thromboembolism Bleeding much more common than thrombotic/thromboembolic events Hemorrhagic stroke most common cause of death in HM II DT trial Mucosal bleeding significant cause for readmission after implantation Pump thrombosis rare usually from clot ingestion or misaligned inflow cannula

13 Patients With Events Event Rate vs INR Values HeartMate II Clinical Study Thrombotic Events Hemorrhagic Events Bleeding Requiring > 6 U Bleeding Requiring Surgery Hemorrhagic Stroke Pump Thrombosis Ischemic Stroke INR Range: < >3.0 Boyle et al AHA 2007

14 Can Axial Flow Pumps Cause Acquired vwf? EJCTS 2008, 33; 4:

15 Nr Gender Age Diagnosis Indication LVAD support vwf: AG 1 vwf: CB 2 vwf:cb/ vwf:ag 3 Loss of largest vwf MM 4 High molecular weight MM 5 PFA C-EPI 6 PFA C-ADP 7 (years) (months) (%) (%) (%vs.pool) (sec) (sec) 1* male 44 CHD BTT yes > 250 > 250 2* male 35 DCM BTT yes > 250 > male 32 DCM BTT yes > 250 > 250 4* male 30 CHD BTT yes 0.4 vs 20.5 > 250 > 250 5** male 23 DCM BTT yes > 250 > 250 6* male 45 CHD BTT yes 14.6 vs 30.5 > 250 > 250 7* male 42 DCM BTT yes > 250 > 250 8* male 16 Myocarditi s BTT yes > 250 > 250 9* male 41 DCM BTT yes 7.3 vs 30.8 > 250 > ** male 64 CHD DT yes 20.9 vs 32.8 > 250 > ** female 52 CHD BTT yes 8.1 vs 33.1 > 250 > ** male 53 DCM BTT yes 5 vs 22 > 250 > ** male 41 CHD BTT yes 15.1 vs 24.7 > 250 > * male 28 DCM BTT yes > 250 > male 60 CHD DT yes 6.2 vs 14.8 > 250 > ** male 58 DCM BTT yes 3.5 vs 24.7 > 250 > * male 53 CHD BTT yes > 250 > male 54 CHD DT yes > 250 > ** male 57 DCM BTT yes 5.1 vs 35.5 > 250 > ** male 36 CHD BTT yes 5.9 vs 26.6 > 250 > ** male 45 CHD BTT yes 8.1 vs 25.2 > 250 > * male 64 DCM BTT yes > 250 > * male 40 CHD BTT yes > 250 > * female 46 DCM BTT yes 5.4 vs 24.7 > 250 > ** male 50 CHD DT yes 1.6 vs 34 > 250 > 250

16 vwf diagnostics after removal of HM II Nr Time after vwf:cb/ Ex/Tx vwf:ag 1 vwf:cb 2 vwf:ag 3 Loss of largest vwf MM 4 High molecular weight MM 5 PFA C-EPI 6 PFA C-ADP 7 Platelet H c t 8 CRP 9 (months) (%) (%) (%vs.pool) (sec) (sec) (1,000/u l) (%) (mg/l) no 56.5 vs no 20.1 vs no 24.6 vs 26.1 n.d. n.d no n.d. 69 n.d no n.d no n.d no 30.4 vs no 26.5 vs no 33.2 vs no 30.4 vs no 27.8 vs no 34.1 vs

17 2nd analysis in ongoing HMII patients Nr Time after vwf:cb/ first test vwf:ag 1 vwf:cb 2 vwf:ag 3 Loss of largest vwf MM 4 High molecular weight MM 5 PFA C-EPI 6 PFA C- ADP 7 Platelet Hct 8 CRP 9 (months) (%) (%) (%vs pool) (sec) (sec) (1,000/u l) (%) (mg/l) yes 10.9 vs yes 8.7 vs 23.3 >300 > yes 9.2 vs 31 >300 > yes 6.3 vs 21.4 >300 > yes 16.5 vs 25.1 >300 > yes 1.2 vs 17.8 >300 > yes 7.6 vs 27.6 >300 > yes 7.2 vs 25.2 >300 > yes 9.5 vs 33.7 >300 > yes 7.3 vs 23.6 >300 > yes 9.2 vs

18 vwf is it the Cause or Contributor to Mucosal/GI Bleeding

19 Indications? BTT DT Myocardial Recovery Advanced heart failure, inotropic dependent with end-organ dysfunction

20 Contemporary Outcomes with the HeartMate II LVAS CMS National Coverage Meeting for Destination Therapy May 12, 2010

21 U.S. HMII DT Primary Cohort N Engl J Med 2009; 361:

22 HeartMate II Destination Therapy Trial Design Prospective, randomized, multicenter clinical trial Inclusion criteria: LVEF 25% Peak VO2 <14 ml/kg/min (or 50% age- and sex-predicted) And either NYHA class IIIb-IV symptoms for at least 45 of the prior 60 days on maximally tolerated oral heart failure medications, or Dependence on IV inotropes for at least 14 days, or Dependence on an IABP for at least 7 days Not a candidate for transplantation Exclusion criteria: Irreversible renal, pulmonary or hepatic dysfunction or active infection

23 Defining the Patient Cohort Included Definitions: in the HMII DT Trial Class IIIB: Cardiac disease resulting in marked limitations of physical activity. Patients are comfortable at rest. Mild physical activity causes fatigue, palpitation, dyspnea, or anginal pain. Class IV: Cardiac disease resulting in inability to carry on any physical activity without discomfort. Symptoms of cardiac insufficiency or of the anginal syndrome may be present even at rest. If any physical activity is undertaken, discomfort is increased.

24 HeartMate II DT Trial Exploring the Differences Between Class IIIB and IV Patients Class IIIB (n=160) Class IV (n=407) p Mean Age (yrs) 63 ± ± Female (%) Ischemic (%) Treatment (%) Digoxin Beta blocker CRT Inotropic Therapy IABP < Serum sodium (mmol/l) Pre-albumin (mg/dl) Creatinine (mg/dl) Hct (%) WBC (x10 3 /ml)

25 HeartMate II DT Trial Exploring the Differences Between Class IIIB and IV Patients NYHA Class IIIB (n=160) NYHA Class IV (n=407) n Mean SD Median n Mean SD Median P* PCWP (mmhg) Systolic PA (mmhg) Diastolic PA (mmhg) Mean PA (mmhg) CVP (mmhg) Cardiac Index (l/min/sqm) Cardiac Output (l/min) PVR (Wood Units) Systolic BP (mmhg) Diastolic BP (mmhg) LVEF % *Unpaired t-test

26 HeartMate II DT Trial Exploring the Differences Between Class IIIB and IV Patients Patients Discharged on Support (%) Class IIIb Class IV Median days to Discharge Class IIIB Class IV Median Duration of Support (days) Class IIIB Class IV

27 What is REVIVE-IT? Randomized Evaluation of VAD InterVEntion before Inotropic Therapy NHLBI RFP Joint NHLBI/Industry support Solicitation July 2009 Submission Dec 2009 Cleveland Clinic/Duke (sponsor Thoratec) Michigan/Pittsburgh (sponsor HeartWare) Award pending REVIVE-IT Trial Design

28 REVIVE-IT Solicitation Study Hypothesis VAD will improve functional 12 mo All cause mortality VAD will not exceed that of the OMM REVIVE-IT Trial Design

29 REVIVE-IT Solicitation Inclusion Criteria (to achieve estimated mortality in OMM arm of 1 yr) NYHA Class IV or Advanced III Not a transplant candidate LVEF 35% Duration of HF 1 year Maximal evidence based Rx 3 months Hospitalization in past 6 months No inotropic support within prior 6 months Peak VO % of predicted peak VO 2 REVIVE-IT Trial Design

30 Study Design REVIVE-IT Solicitation RCT between VAD and OMM arms 1:1 randomization, 50 patients per group Primary composite endpoint Survival Functional status 20% improvement, objectively assessed Primary outcome assessed at 1 year REVIVE-IT Trial Design

31 REVIVE-IT Solicitation Secondary endpoints Safety Secondary functional and physiological markers QOL Neurocognition Cost and cost-effectiveness 2 year follow-up REVIVE-IT Trial Design

32 LVEF 30% Key Issues in REVIVE-IT Identification of Sample with 30% 1-yr Mortality CCF/Duke Peak VO 2 14 ml/kg/min or < 50% age- and sexpredicted 6 min walk distance < 300 m Minn. Living with Heart Failure Score 60 or KC Cardiomyopathy Score 40. UM/Pitt LVEF 35% Peak VO 2 14 ml/kg/min ( ) or 16 ml/kg/min ( ) AND < 55% age- and sexpredicted Seattle Heart Failure Model score 1.5 REVIVE-IT Trial Design

33 Key Issues in REVIVE-IT Identification of Sample with 30% 1-yr Mortality CCF/Duke Hospitalization within prior 6 months UM/Pitt No requirement for hospitalization SHFM independent of recent hospitalization (ACCLAIM) REVIVE-IT Trial Design

34 Seattle Heart Failure Model Age > 60, NYHA III, creat 2.5, LVEF 35% N=3238 N=3238 pts from PRAISE, ValHeFT and ACCLAIM

35 SHFM vs. Peak VO 2 Superiority of SHFM for Risk Stratification Peak VO strata for pts with SHFM=2 SHFM 0-3 for pts with N=3238 peak VO For SHFM =2, peak VO2 provides no additional risk stratification SHFM discriminates further among pts with peak VO REVIVE-IT Trial Design

36 TAH: Is there a clinical need?

37 TAH: Is there a clinical need?

38 Long-Term MCSS at DHZB New Concepts BIVENTRICULAR HEART ASSIST HeartWare LVAD Modification for Clinical RVAD Banding of the Pulmomary Artery Graft Pressureadaptation HeartWare RVAD HeartWare LVAD

39 Long-Term MCSS at DHZB New Concepts BIVENRTICULAR HEART ASSIST WITH CENTRIFUGAL BLOODPUMPS Study 1 HeartWare HVAD DHZB Pat HW 6

40 BIVENRTICULAR HEART ASSIST WITH CENTRIFUGAL BLOODPUMPS Study 1 HeartWare HVAD DHZB Pat HW 6

41 HeartWare Biventricular Support

42 Successful Design Miniaturization

43 Mock Circulation Study [1] Left Ventricle [2] Right Ventricle [3] Aorta [4] Pulmonary Artery [5] Systemic Resistance [6] Pulmonic Resistance [7] Systemic Compliance [8] Pulmonic Compliances Measurements 1. AoP, LVP, LAP 2. PAP, RAP, RVP 3. BiMVAD (Q, rpm, power) 4. AoF, PAF 5. LVV, RVV Simulated Test Conditions 1. Normal 2. BiV Failure 3. Hypotension 4. Hypertension 5. Hypovolemia Protocol 1. Baseline (no support) 2. Low (< 1.5 lpm) 3. Moderate (2-3 lpm) 4. Maximal (> 5 lpm) 5. Baseline (no support)

44 Mock Circulation Study

45 Acute Animal Study (n=3) Measurements 1. AoP, LVP, LAP 2. PAP, RAP, RVP 3. BiMVAD Flows, RPM, power 4. AoF, PAF 5. LVV, RVV 6. CBC, LDH, PfHb Test Conditions Protocol 1. Normal 1. Baseline (no BiMVAD) 2. BiV Failure (Esmolol) 2. Low support (< 1.5 lpm) 3. Hypotension (Nitroprusside) 3. Moderate support (2-3 lpm) 4. Hypertension (Phenylephrine) 4. Maximal support (> 5 lpm) 5. Hypovolemia (volume reduction) 5. Baseline (no BiMVAD 6. Fibrillation (electrical)

46 New Trends and Indications for LVADs VADs have improved outcomes out to 2 yrs and are the treatment of choice for end-stage heart failure Improved outcomes resulting in studies to evaluate earlier implantation Blood trauma and bleeding needs additional investigation CF VADs can be used for chronic biventricular support

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