QUEST FOR ULTIMATE CURE

“MODEL T” to “DREAM THERAPY”

Where is the MIRACLE BULLET?

Chittoor B. Sai Sudhakar, MD, FRCS

The Holy Grail !!!!!!!!

Treatment of Symptomatic CHFTreatment of Symptomatic CHF

5 classes of drug

ACE inhibitors

Beta blockers

Aldosterone antagonist

Nitrates and Hydralazine

Angiogenesis II receptor blockers

First Device as BTTFirst Device as BTT

Designed by Dr. Domingo Designed by Dr. Domingo Liotta, 1969 Liotta, 1969

This heart was the first to be This heart was the first to be implanted in a human being implanted in a human being as a bridge to transplant by as a bridge to transplant by Dr. Denton A. Cooley. Dr. Denton A. Cooley.

The patient survived for The patient survived for almost three days with the almost three days with the artificial heart and 36 hours artificial heart and 36 hours more with a transplanted more with a transplanted heart.heart.

Jarvik-7Jarvik-7

Drs. Willem Kolff, Drs. Willem Kolff, Donald Olsen, and Donald Olsen, and Robert Jarvik Robert Jarvik

First human implant First human implant 19821982– Destination TherapyDestination Therapy

200 patients bridged 200 patients bridged (Jarvik-7/Symbion)(Jarvik-7/Symbion)

Heartmate XV & XVEHeartmate XV & XVE

Has been the workhorse for a long time

Does not need anti-coagulation

Bulky

Lasts for a 12-24 months

Our record is 32 months and going

REMATCH Trial

(Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart failure)

Inclusion criteria resembled those for Heart TX

Class IV CHF

LVEF <25%

Peak oxygen consumption <12-14ml/kg/min

Inotrope dependent

Stevenson, L. W. et al. Circulation 2003;108:3059-3063

Profiles of HF in different trials

REMATCH patients were much sickerGroup intermediate in severity between Status I & II

heart transplant candidates

REMATCH Survival

LVAD 60% 49% 28%

OMM 39% 24% 11%

6 mth 1 year 2year

Inotrope dependent at randomization – 91pts

Not on inotrope at randomization – 38pts

LVAD 61% 57%

OMM 67% 40%

Heartmate IIHeartmate II

VentrAssistVentrAssist

298 gms, 6 cms, size of a hockey puck

Single moving part – hemodynamically suspended impeller

Electromagnetic field rotates the impeller

HeartWareHeartWare

Miniaturized centrifugal pump

Totally Intrapericardial

Single moving part and no mechanical bearings

Long Term SupportLong Term Support

0

10

20

30

40

50

60

Proce

dure

s

New P

atie

nts

Pump E

xchan

geHM

II

HM X

VE

Ventra

cor

HeartW

are

IVAD

Cpulse BTT

DT

Recove

ry

2005

2006

2007

2008

2009

The difficult part is the

selection

Patient Profile/ Status: INTERMACS Levels

1. Critical cardiogenic shock

2. Progressive decline

3. Stable but inotrope dependent

4. Recurrent advanced HF

5. Exertion intolerant

6. Exertion limited

7. Advanced NYHA III

INTERMACS: Patient Selection

PROFILE-LEVELPROFILE-LEVEL # Pts# Pts

Yr 1Yr 1

Official ShorthandOfficial Shorthand General time frame General time frame for supportfor support

INTERMACSINTERMACS

LEVEL 1LEVEL 1

8282 ““Crash and burn”Crash and burn” HoursHours

INTERMACSINTERMACS

LEVEL 2LEVEL 2

8181 ““Sliding fast”Sliding fast” Days to weekDays to week

INTERMACSINTERMACS

LEVEL 3LEVEL 3

1818 Stable but Stable but DependentDependent

WeeksWeeks

INTERMACSINTERMACS

LEVEL 4LEVEL 4

99 ““Frequent flyer”Frequent flyer” Weeks to few Weeks to few months, if baseline months, if baseline restoredrestored

INTERMACSINTERMACS

LEVEL 5LEVEL 5

44 ““Housebound”Housebound” Weeks to monthsWeeks to months

INTERMACSINTERMACS

LEVEL 6LEVEL 6

33 ““Walking wounded”Walking wounded” Months, if nutrition Months, if nutrition and activity and activity maintainedmaintained

INTERMACSINTERMACS

LEVEL 7LEVEL 7

44 Advanced Class III Advanced Class III

Stevenson, L. W. et al. Circulation 2003;108:3059-3063

Definition of heart failure populations with decreasing estimated mortality

Seattle Heart Failure ModelSeattle Heart Failure Model

Right Heart Failure predictorRight Heart Failure predictor

Elevated CVP is the single most important factor

Other factors:PA pressuresRVSWRVSWIDegree of RV dysfunctionTricuspid Annular Excursion

Even more difficult : post-

op management

INTERMACSINTERMACS

Kirklin JK, et al. J Heart Lung Transplant ; 2008:1065-1072

50 YO M ICM50 YO M ICM

Heartmate XVE placed 4/13/06Heartmate XVE placed 4/13/06– Complicated by persistent Enterococcus Complicated by persistent Enterococcus

bacteremiabacteremia

Replaced with Heartmate XVE 11/2/06Replaced with Heartmate XVE 11/2/06– Infection cleared, was doing wellInfection cleared, was doing well

Admitted 3 months later because high Admitted 3 months later because high power utilization and batteries burning out power utilization and batteries burning out

Case ReportCase Report

M. Firstenberg

LVAD ThrombosisLVAD Thrombosis

M. Firstenberg

LVAD ThrombosisLVAD Thrombosis

M. Firstenberg

VAD endocarditisVAD endocarditis

M. Firstenberg

VAD ThrombosisVAD Thrombosis

LOH 4 monthsPost-op

Migration

GF 10days post-op

Migration

Lead Fractures : Multi-Institutional ExperienceOSU, St. Vincent’s (Indiana), U of Minnesota

HIGH TECH PROBLEM!!!!!

Lead fracture in Ventrassist

LOW TECH SOLUTION

Other therapies – Immune AdsorptionOther therapies – Immune Adsorption

Several antibodies against the cardiac proteins

IA removes these antibodies

9 patients in each arm

High anti beta-1 adrenoceptor auto antibodies

IA for five courses followed by IgG substitution

Improvement in functional class at 3 months

Immune Adsorption

In our lab at OSU

Ovine model of heart failure

Embolization techniqueBeads

Aggregated platelets

LAD ligation

Picture 1. Fluoroscopy picture of left circumflex artery cannulated with 6F catheter and injected with 90um polyester micro beads

CytokinesCytokinesThrombus Thrombus embolizedembolized Bead embolizedBead embolized LAD ligatedLAD ligated

GFR alpha-3GFR alpha-3 53225322 47644764 16091609

MIGMIG 50925092 25052505 17391739

IL-1 alphaIL-1 alpha 49834983 44874487 28152815

TGF-beta 1TGF-beta 1 46814681 25802580 12821282

IL-15IL-15 46614661 36733673 25362536

IFN-gammaIFN-gamma 40874087 23022302 13481348

IL-3IL-3 40874087 15721572 19611961

IL-13IL-13 38573857 5454 16221622

GROGRO 34163416 22622262 19141914

MCP-1MCP-1 29882988 22752275 18211821

IFN-alpha / beta R2IFN-alpha / beta R2 28782878 22262226 666666

MCP-2MCP-2 26892689 11 342342

Fas / TNFRSF6Fas / TNFRSF6 24122412 23882388 13441344

ICAM-1ICAM-1 21092109 11 671671

EpiregulinEpiregulin 21032103 18261826 483483

Cytokine Expression

Chandrakala

Our ongoing InvestigationOur ongoing Investigation

Autoantibodies to CEC & ERP

Inhibit the homing mechanisms of BM derived EPC

Inhibition of Angiogenesis, Neovascularization and Repair

Are there any magic bullets for cure out there?

If there is one then we can sing praises:

Shot through the heart, you give VAD a bad name

Thank you