RECENT ADVANCES IN MECHANICAL CIRCULATORY SUPPORT

1
(No Transcript)
2

• Ventricular Assist Devicesand Other Surgical
  Optionsfor Advanced Heart Failure
• Jaime Moriguchi, MD
• Ahmanson-UCLA Cardiomyopathy Center
• Los Angeles, California

3
The Burden of CongestiveHeart Failure

• 5 million Americans with CHF 550,000 newly
  diagnosed / yr
• 70,000 NYHA Class IV (Class D)
• lt 2,400 heart transplants / yr in U.S.
• 20 die waiting overall 300,000 deaths/yr
• Increasing waiting period critically ill
  recipients poor outcome
• Increasing reliance on mechanical circulatory
  support as bridges
• Search for permanent devices as alternatives to
  transplantation or destination therapy

4
a
b

c
Figure 1 Recent trends in supply and demand for
donor hearts a) number of patients on UNOS
waiting list at year end b) number of
transplants per year reported by UNOS c)
mortality among patients listed
5
Indications for Mechanical Circulatory Support

• Failure to wean off CPB (post-cardiotomy)
• ESHD awaiting Tx failing optimal medical
  management
• Acute viral myocarditis/post-partum
  cardiomyopathy (BTR)
• Acute Massive MI w/ shock
• ? Cardiac arrest
• Destination therapy for non-Tx

6
Hemodynamic Criteria for Mechanical Circulatory
Support

• Unacceptable hemodynamics despite optimal medical
  management
• CI lt 2.0 l/min/m2
• RA gt 20 mm Hg
• Pcwgt 20 mm Hg
• Persistent hypotension (SBP lt 80) despite 2 or
  more inotropes/IABP
• End-organ hypoperfusion/oliguria/rising
  Cr./metab. acidosis/abn. LFTs/altered MS
• Marginal hemodynamics w/ anticipated long waiting
  period (high PRAs/O blood type/lgBSA)

7
Exclusion Criteria For Mechanical Circulatory
Support

• Multi-system or irreversible organ failure
• Uncontrolled infection / sepsis
• Recent pulmonary infarction
• Significant bleeding diathesis
• Recent / significant neurologic insult
• No reasonable long-term options
• Hx of non-compliance / inadeq. social support
• Advanced age (? gt 80 yo)
• Malignancy

8
Device Selection

• Duration of support
• Size of patient
• Severity of LV dysfunction
• Need for bi-ventricular support/organ recovery
• Intended use (BTR / BTT / DT) FDA restrictions
• Cause of ventricular failure / likelihood of
  recovery
• Surgeon experience / preference
• Bleeding issues / long term anticoagulation
• Cost issues

9
MCS Complications(Early)

• Bleeding / Re-exploration
• Renal Failure
• Pulmonary Hypertension
• RV failure
• Hypoxemia (PFO / ASD)
• Thrombo-embolic events
• Arrhythmias
• Infection

10
MCS Complications(Late)

• Thrombo-embolic events (CVA)
• Infection (driveline / device endocarditis)
• Respiratory failure
• VAD thrombus
• Cachexia / Ileus / gastric compression (HM)
• Hemolysis (axial)
• Arrhythmias
• Inflow / Outflow obstruction

11
RV Failure

• Risk factors
• Excessive blood products / bleeding
• Pulmonary hypertension ( thromboxane / PRBCs)
• Prolonged CPB time
• RCA occlusion / inadequate preservation
• LVAD induced change septal geometry / function
• Management
• Minimize blood products
• Reduce PAPs (NO / Nesiritide)
• Inotropes (dobutamine / milrinone / isuprel)
• Reduce LVAD flow
• CVVH
• RVAD
• Incidence 10 20

12
Keys to SuccessfulCirculatory Support

• PATIENT SELECTION
• Timing of implantation
• Meticulous surgical technique (minimize bleeding
  / blood products)
• Appropriate device selection (tailored to
  patients needs)
• Management of PHtn / avoid RV failure
• Vigilant postoperative management

13
Ventricular Assist Devices

• Paracorporeal
• Systems

14
Abiomed BVS 5000

• Class external pulsatile
• Common use short-term LVAD, RVAD, or BiVAD
• Indications
• post-cardiotomy
• VAD support transport to tertiary facility
• acute MI/myocarditis
• RVAD w/ implantable LVAD
• Limitations
• short-term, ICU only
• heparin required

15
Console Drives BVS 5000 and AB5000
AB5000 Ventricle
BVS 5000 Blood Pump
16
Thoratec The Versatile VAD System

• Only FDA approved VAD for
  both Transplant and Recovery
• Univentricular or Biventricular
• Numerous Cannulation Options
• Small / Large Patients (17kg
  90kg)
• Short Long term
  support

17
(No Transcript)
18
Thoratec TLC-II Portable Driver
CIRCULATORY SUPPORT
PRODUCTS Small, portable replacement for the
Dual Drive Console Lightweight 9.8 kg

(with batteries
and carrying case) Rechargeable batteries
European clinical use and CE Mark U.S.
clinical trial ongoing
19
Ventricular AssistDevices

• Implantable
• Systems

20
Future VAD ProductsThoratec Implantable VAD
System
Thoratec IVAD approved for use in United States
August 6, 2004
21
Future Thoratec VAD ProductsPortable
Implantable VAD System
Implantable VAD

TLC-II Portable VAD Driver
22
HeartMate LVAS Unique Technology

• Textured surfaces result in TE rates of only 3
  (IP) 6 (VE)
• Systemic anticoagulation not required

23
HeartMate Vented Electric (VE) LVAS

• Patient 37 year-old ophthalmic surgeon
• Ischemic CMY
• Implant duration 220 days
• Returned to work 45 days post-implant
• Outcome successfully transplanted

24
Cost Effectiveness
Comparison of costs for patients with and
without HeartMate LVAS
ICU 3400/day, step down 900/day Accounts
for cost of LVAS, 40,000 for implant surgery,
transfer of LVAS patient to step down unit 1 week
post-implant and discharge of electric system
patient at 3 weeks.
25
New Therapeutic Applications
Ventricular Recovery

• REMATCH
• Randomized
• Evaluation of
• Mechanical
• Assistance for the
• Treatment of
• Congestive
• Heart failure

• Mechanisms
• ventricular unloading
• cardiac rest
• myocyte recovery

Use of HeartMate LVAS for ventricular recovery is
only approved outside the US.
26
Rematch Trial Results

• N129 LVAD (68) Medical Rx (61)
• NYHA IV Non-Tx Candidates
• 48 reduction of all-cause mortality w/ LVAD RR
  .52 P 0.001
• Survival _at_ 1 yr 52 (LVAD) 25(Med)
• _at_ 2 yrs 23 (LVAD) 8 (Med Rx) P0.09
• First randomized study to demonstrate
  superiority of assist dev. over medical therapy
• 11/6/02 - FDA approves VE HeartMatefor
  destination therapy

27
Improved Outcomes in 2-year LVAD Survival
43
32
23
21
10
9
8
8
6
0
As Treated Analysis as of December 2003 dataset
28
Destination Therapy

• Indications
• NYHA FC IV (Class D) despite OMM gt 60 of last
  90d
• Tx ineligible w/ life expectancy lt 2 yrs
• LVEF lt 25
• Peak VO2 lt 12 ml/kg/min or inotropic/IABP
  dependence
• Contraindications
• BSA lt 1.5 m2
• Performed at CMS-approved Centers
• 142 patients implanted as DT (10-1-04)
• Median LOS 33d (29d for REMATCH)

29
Novacor LVAS Principle

• The pump is implanted within the abdominal wall
• Accepts blood from the left ventricle, allowing
  the natural LV to act as an atrium
• Outflow conduit anastamosed to ascending aorta
• Flexible percutaneous lead provides vent and
  connection to wearable controller battery packs

30
Worlds Longest MCS Patient (5.6 years)
Giordano Luppi, 67 years, Novacor implantation on
13. Feb. 1998 in Verona, elective pump exchange
on 12. March 2002. Lives in a small town with his
wife Anna. Leaves home every morning at 430 to
open the familiys Bar and to prepare the
breakfast (Cappuccino and Brioches). He lives a
happy and normal life!
31
LVAD Patients Lead Active Lives
32
UCLA VAD Experience

• Total VAD implants 145
• Implantable VADs 84
• Heartmate IP / VE 14 / 12
• Thoratec BiVAD 30
• Thoratec LVAD 18
• Novacor/Toyobo
  3 / 5
• Jarvik 2000/AbioCor 2 / 1
• Survival to Tx/destination 50/79
  (63)
• Survival to Tx w/ Thoratec 34/46
  (74)
• 30d 1 yr survival post-Tx 93

2 ongoing Thoratec VADs / 2 HeartMateVEs
October 7, 2004
33
(No Transcript)
34
Factors Leading to Prolonged Waiting Periods for
LVAD Patients

• Large body size
• Type O-blood
• Pre-sensitization (development ofpre-formed
  antibodies)
• Cardiac cachexia / malnutrition / healing
• Infection
• Multi-organ dysfunction
• Heparin associated platelet antibodies

35
(No Transcript)
36
ContinuousNon-PulsatileFlow Devices
37
Implantable Continuous Flow VADs

• Advantages Simple, single moving part, no
  valves, low energy requirements, smaller device
  size, lower cost, lower implant morbidity,
  possible thoracotomy off-pump approach.
• Potential disadvantages Nonpulsatile flow- ?
  organ recovery, need for chronic anticoagulation,
  aortic insuff with device failure, limited flow,
  ? inc. risk of thrombus formation, hemolysis.

38
(No Transcript)
39
Jarvik 2000 Features

• True booster pump function - pulsatility from LV
  contraction(3- 10 l/min) with afterload reduction
• Intraventricular placement
• No pump pocket inflow cannula lower TE rate
• Avoids tethering apex
• All analog controller, single moving part
  ergonomically efficient

40
Freiburg, 8/01
41
(No Transcript)
42
DeBakey VAD
43
Future VAD Products HeartMate II LVAS
Technology Benefits

• High Speed Rotary
• Textured Blood Contacting Surfaces
• Automated Control (physiological response)
• Potential Pulsatility
• Quiet
• Long Life
• Valveless
• Small

1st successful implant _at_ THI Nov 2003
7 / 10 w/ stator thrombosis change to smooth
surface
44
HeartMate III Features

• Centrifugal
• Magnetically Levitated Rotor (bearingless)
• HeartMate Textured Surfaces
• Fixed Speed, Auto Speed, and Pulse Mode
• Flow 2-12 l/min
• Potential extended longevity (gt10 yrs)

45
Role of LVADs inMyocardial Recovery

• Improved contractile strength (force frequency
  relationship)
• Normalization of myocyte Ca transient
• Upregulation of genes encoding Ca cycling
  proteins (SER CA2a, RyR, Na-Ca exch.)
• Nl of cytokines, MTP II, IX, annexin, ANF
• Improvement in LVEF/Reduction LVEDD
• Hemodynamic/VO2 max

46
LVADs Bridge to Recovery

• Etiology viral myocarditis, p-partum,
  postcardiotomy
• Recent onset, shorter duration, smaller
  ventricular dimensions
• LVAD weaning strategies (fixed v auto mode)
• BTR success rate 5 10 explanted
• Clembuterol (M. Yacoub)
• Unique B-receptor antagonist / stim. insulin GF
• 10/19 explanted 2.5 yr EF 60 mech? recruit
  progenitor cells
• Combination therapy
• Cell transplantation

47
Surgical Management ofAdvanced Heart Failure

• High risk revascularization (PET/DSE)
• LVEDD lt 40 mm/m2
• LVEF gt 25
• 2 or more areas of discordance (PET)
• Vascular targets
• Ventricular remodelling
• Batista procedure
• Dor / SAVR procedure
• Mitral valve repair / replacement (Bolling)
• Passive restraint devices

48
RESTORE (Dor) Procedure

• 1198 pts w/ ischemic CMY
• Prior anterior MI w/ akinetic-dyskinetic seg.
• Class III (40) IV (24)
• Mean LVEF 28 LVESVI 96 ml
• Endoventricular circular patchplasty
• Revascularization / mitral repair / MVR
• Objective Reconstructive Endoventricular
  Surgery restoring Torsion Original Radius
  Elliptical shape

49
RESTORE (Dor) Procedure for Ischemic
Cardiomyopathy

• Low Operative Risk
• Improved EF (28 40)
• Decreased LVESVI (96ml 62ml)
• High Survival at 3 yr 83 5 yr 69
• Low CHF Readmission (11)
• NYHA Class I II Post-op

50
Acorn CorCap Support Device

• Unique fabric (polyethylene)
• Designed to support/reshape heart
• Reduce diastolic wall stress/remodelling
• Restrict ventricular dilatation
• Pivotal randomized trial n300
• 81 Cl III Mortality/EF NS
• CSD greater red LVED/SV
• CSD improved QOL/red. proc.

51
The TotalArtificialHeart
52
AbioCor Artificial Heart

• Class totally implantable heart replacement
• Common use long-term
• Indications
• bridge to OHT
• alternate recipients/elderly
• destination therapy (elderly)
• Limitations
• no biological back-up
• coumadin required

53
ROBERT TOOLS1ST AbioCor Recipient

• Implanted 7/2/01 Ischemic cmy/shock
• AbioScore 91 severe malnutrition/ARF
• Multiple GI bleeds
• Subtherapeutic INR (80)
• Complete end-organ recovery
• Ambulatory/numerous excursions
• TIA (d63) CVA (131)
• Died MSOF postop 151

54
AbioCor Summary of Results

• 14 patients have received the AbioCor
• Majority implanted at Louisville Humana Medical
  Center (Gray Dowling) THI
• Longest period of support 520 d (TC)
• Last 2 (13 14) doing well
• Most frequent complication bleeding /
  thromboembolism
• Membrane durability concerns

55
AbioCor
Source of thrombus
Left atrial cage
56
Tom Christerson AbioCor Recipient 2
57
Conclusions

• Successful circulatory assistance depends upon
  appropriate patient selection
• Early transfer to tertiary center for VAD
  implantation can reduce end-organ dysfunction,
  improve survival reduce costs
• Select center w/ array of devices tailored to
  patients needs back-up high risk
  revascularization / adv. HF surgery
• LVADs utilized as destination therapy should be
  considered for nonTx candidates and may provide a
  viable long term option as an alternative to
  transplantation

58
Mechanical Circulatory Assistance Heart
ReplacementFuture Directions

• Increasing use of implantable (HeartMate) devices
  for destination therapy (est. 50-100,000/yr)
• Earlier implantation of continuous
  (non-pulsatile) VADs for destination as well as
  recovery in patients w/ residual LV function
• (?)Potential use of TAH / IVAD / CARDIOWEST for
  ESHD as an alternative to transplantation
• Research in genetic engineering/cloning
  techniques will lead to development of fully
  functional biological replacement hearts
  genetically identical to recipient

59
Genetically Cloned vsArtificial Heart
60
Thank You!
THE END