Alfred Blalock M.D.

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Alfred Blalock M.D.
1899-1964
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Internship / Johns Hopkins Hospital
1961
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Internship / Johns Hopkins Hospital
1961
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A Unifying Approach to Dilated Cardiomyopathy
from Many Causes

• Gerald D. Buckberg M.D.
• Division of Cardiothoracic
  Surgery
• David Geffen School of Medicine at
  UCLA

Crafoord Lecture Stockholm
2009
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AATS / STS Meetings
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Future

• Sulk Assault by catheter based
  technology
• Smile Innovate new pathways
• Surgical Restoration
• of CHF Geometry

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Congestive Heart Failure

• Form / Function Relationship Revisited
• A Unifying Concept

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CHF Decision Tree

• Option Understand Normality
• Disease Distort Normality
• Goal Rebuild Normality

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Hypothesis Abnormal Ventricular Structure /
Function Relationshipcauses CHF
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Heart Shape
Dilated ( sphere )
Normal ( ellipse )
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TRATTATO DELLA STRUTTURA DEL CUORE DELLA SUA
AZIONE E DELLE SUE INFERMITA SENAC
L.M. MDCCLXXIII
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Form / Function Relationship

• Twisting Motion
• Conical Configuration

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Normal Heart
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Mahajan, 2007
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Cardiac Tagging(Deformation)
cine
tagging
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Bogaert, AJP, 2001
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Ejection Fraction
Apex
Apex
Bogaert, AJP, 2001
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Myocardial Strain
Bogaert, AJP, 2001
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Dilated Cardiomyopathy
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ß
Ventricular Restoration Rebuild ellipse
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Ventricular Dilation Post MI
Dyskinesia
No reflow
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Ventricular Dilation Post MI
Akinesia
A New Target
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CHF Surgical ObjectivesTriple V

• Vessels Remote from MI
• Valve Geometric MR
• annulus size
• inter-papillary
  width
• Ventricle Spherical shape

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R econstructive E ndoventricular S urgery,
returning T orsion O riginal R adius, and E
lliptical Shape to the LV
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RESTORE Evolution
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RESTORE GROUP

• Birmingham, AL
• Athanasuleas / Stanley
• John Kirklin
• Los Angeles, CA
• Buckberg / Moriguchi
• Cleveland, OH
• McCarthy / Young Starling
• Blackstone
• New York, NY
• Oz / Burkhoff
• Charlottesville, VA
• Kron / Bergin
• Orlando,Florida
• Scott / Accola
• 
  

• St. Louis, MO
• Kouchoukos / Cole
• Monte Carlo, Monaco
• Dor / DiDonato
• Bordeaux, France
• Fontan
• Freiburg, Germany
• Beyersdorf
• Milan, Italy
• Menicanti / Santambrogio
• Sao Paulo, Brazil
• de Oliveira / da Luz
• Kanagawa, Japan
• Suma / Isshiki

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Surgical Ventricular RestorationSVR

• Patient Selection ( n 1198 )
• Q wave anterior infarction
• Apical / septal akinesia or dyskinesia
• Age
• range 25 - 89
• mean 63 /- 10.7

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Dilated Ischemic Cardiomyopathy
SVR
Levy D. NEJM 2002
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Ventricular Restoration
preop
postop
E.F. 22 LVESVI 102ml/min/m2
E.F. 64 LVESVI 28 ml/min/m2
V Dor 2003
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Longitudinal Strain
Pre SVR
Post SVR
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Follow-up NYHA Functional ClassPre operative

NYHA 2.9 III IV 67
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Follow-up NYHA Functional ClassPost operative

NYHA 1.7 III IV 15
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SVR for Ischemic Cardiomyopathy

• Low Operative Risk
• Improved EF
• Decreased LVESVI
• High Survival at 5 years
• Low CHF Readmission
• NYHA Class I II Post-op

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CHF Survival Registry Data
SVR
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SVR
?
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CABG
Framingham
Athanasuleas CL JACC 2004, Shah PJ JTCVS,
2003, Levy D NEJM, 2002
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Coronary Bypass Surgery with or without
Ventricular Restoration

• Surgical Treatment for Ischemic Failure
• STICH

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• STICH Trial tests SVR Concept
• Evidence Based Medicine requires
• Creditable Evidence

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Post MI Dilated Cardiomyopathy Natural
History

• Left Ventricular Volume is surrogate
• for Mortality
• Klein, Gorlin,Circ. 1967, White, Circ.
  1987, Christian, AJC 1991

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STICH vs. prior SVR Reports

• SVR reduces LV Volume
• 7000 patient Registry confirmation
• End systolic volume not EF is
  critical
• STICH studied 490 patients
• Measured volume in 33 ( 161 pts.)
• SVR not better than CABG

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STICH vs. prior SVR Reports

• Is SVR concept improper ?
• Is STICH Trial execution improper ?

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SVR procedure

• SVR Reports (1603 pts)
• Reduce volume 30-58
• STICH
• Reduce Volume 19
• Responsible Procedure
• small LV plication ?
• limited intracavity rebuilding ?

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STICH SVR Flaws

• Original Actual
• ALL gt35 akinesia /
  50 had akinesia /
  dyskinesia
  dyskinesia
• ALL documented necrosis Not reported
• Volume by CMR
  Volume by Echo

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STICH SVR Flaws

• Original
• ALL ESVI measurement
• SVR if ESVI gt 60 ml/m2
• ESVI gt 30 reduction required

• Actual
• ESVI not measured 66
• No ESVI requirement
• ESVI decreased 19

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STICH SVR Flaws

• Original
• 50 centers
• ( 10 cases / center)
• 5 cases / surgeon
• ESVI gt 30 reduction
• required

• Actual
• 127 centers in 26 countries
• ( 4 cases / center)
• 5 cases / surgeon
• ESVI decrease not specified

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Evidence Based MedicineRole of experience

• 
  
• 
  
• 2002 SVR ( ? ventricular volume )
• STICH (n133 / 490)
  -19
• 127 centers
• SVR Reports (n 1603)
  - 40
• 12 centers
• Outcome 2009 Abandon SVR

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STICH SVR Results

• Wrong operation
• Wrong patients
• Wrong Volume Measurements
• Wrong Conclusions Misguide
• 
  Cardiologists

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STICH SVRMisleading End Point Analogy

• CABG unsuccessful
• Open IMA, RCA not grafted
• Hypertension drug unsuccessful
• Inadequate dose used

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STICH Outcomes

• Evidence Based Medicine
• Goals
• were not achieved

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STICH Revisited

• For Meaningful Results
• Exclude all patients with invalid volume
• measurement
• Quantify all patients gt30 reduction by CMR
• Report only patients with acceptable
• volume reduction

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Peak Oxygen Uptake


16
14
12
10
11110
161.5
15.20.8
8
121.3
9.53
6
4
2
0
bpm
Heart Transplant
ml/kg/min
Ventricular Restoration
_at_3 months
Pre op
Post op
Catrufo, 2007
P lt 0.01

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SVR vs. Cardiac Transplant
Conte, 2007
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Economic Considerations

• SVR Cardiac
  Transplant
• Hospital 45,506 137,679
• Drug 2,747
  15,930
• OR 3,748
  11,830
• Drug 2,458
  15,681
• Lab 3,518
  7,219
• Radiology 758
  2,489
• NYHA ( 3 yrs.) 91
  98
• plt0.001

Conte, 2007
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Global CHF ConsiderationsThe Future

• Unifying Geometrical Concept /
• Dilated
  cardiomyopathy
• Ischemic ( scar and diffuse)
• Non ischemic ( idiopathic)
• Valvular ( aortic and mitral regurg. )
• Device therapy ( Bridge to Restoration)
• Cell Biology ( Create surgical scaffold
  / cell Rx)

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Survival / Post SVR LVESVI
lt 30 ml/m2
(n 56)
30-60 ml/m2
(n 12)
gt60 ml/m2
(n 39)
Months
Normal 25 ml/m2
Di Donato, 2001
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Ischemic Disease / Scar

• Disease versus Form
• Decision Process

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Ischemic
Pre op
Post op
Isomura, 2006
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After SAVE operation
After EVCPP operation
Isomura, 2006
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Ischemic DCM (n71)
SAVE elective(n24), Dor elective(n47)
SAVE 80.3
Survival Rate
Dor 77.4
1 2 3 4
From 1998 to 2004
Isomura, 2006
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Diffuse Ischemic Disease

• Dilated heart without scar

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Diffuse Ischemic
Post op
Pre op
Bockeria, 2006
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CABG Viable Akinesia LVESV
(worsens)

PET / Dobutamine
Vanoversheilde , 2000
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CABG Viable Akinesia Wall motion
ESVI ml/m2
lt75

gt75
(worsens)
Vanoversheilde , 2000
PET / Dobutamine
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CABG Viable Akinesia E. F.
ESVI ml/m2
lt75

gt75
(worsens)
Vanoversheilde , 2000
PET / Dobutamine
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Patch implantation
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Microscopic examination of myocardium
Diffuse ischemic
Post Infarction
Massive fibrous scar
Minor intramyocardial fibrosis
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Contractile status after LV restoration
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Evolving Surgical options

• Non ischemic Cardiomyopathy
• Valvular origin
• Mitral or Aortic
  Insufficiency
• Myocyte origin
• Idiopathic Disease

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Natural History Aortic valve replacement
EFlt 40
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Non Ischemic Valvular dilation
Post op ?
Pre op
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Future Surgical Options

• Valve / Ventricular Approach
• Evolving Collaborative Effort

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Non Ischemic Cardiomyopathy

• Myocyte origin
• Has this option been tested ?

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The Dilemma

• Ischemic vs. Non ischemic
• Scar vs. Global Disease ?
• ( prior
  assumption)

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Partial Left Ventriculectomy
(n 506)
Ascione R. J Card Surg 2003
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Partial Left Ventriculectomy24 month data

• 50 survive
• 50 succumb
• Procedure or Concept ?

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Ischemic Cardiomyopathy
( 82)

69
years
n 1198 patients RESTORE
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PVL Cleveland Clinic

• Patients (n62) 12 mos 36
  mos
• Survival 80
  60
• Event Free 49
  23
• LVAD, Transplant
• Franco-Cereceda
  A, et.al, JTCVS 2001121879-893

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PLV Circumferential Shortening
p lt0.01
20
Pre-op
Post op
10
0
Lat. Sept.
-10
Post-op
11/24 survivors ( MRI)
Setser, 2003
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Non Ischemic Cardiomyopathy

• Is diffuse disease
• Uniform or Non Uniform ?

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Myocardial Fibrosis Distribution
Lateral Wall
Septum Normal 0 0 DCM
1911.4 1911.7 (Range) (4-53)
(7-60)
60 random fields
Suma, 2000
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Septum
Lateral Wall
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Non ischemic Cardiomyopathy Extent Fibrosis

• Lateral gt Septum 33
• Septum gt Lateral 28
• Lateral Septum 39

Suma, 2000
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Site Selection Non ischemic cardiomyopathy
Suma,2001
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Pacopexy
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SAVE PROCEDURE (Suma)
Pacopexy
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Pre-op
Post-op
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Dilated Cardiomyopathy

• Ischemic Exclude scar
• Non ischemic Site select damage,
• Exclude
  identified site
• Batista (PLV)
• Pacopexy

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Elective vs. Urgent and Site selection
Site selected
(n61)
Emergent (n21)
Suma,2001
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Left Ventriculoplasty and Mitral Procedure for
Idiopathic DCM

81.8
73.7
Inotropes (-)
62.9
55.3
Plt0.001
Survival rate
37.3
28.0
Inotropes ()
n
46 15
24 9
9 5
62 33
Postoperative months
Suma, 2006
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SVR / NYHA Status
Athanasuleas, et al. JACC 2004441439
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High Risk CHF Patients

• Mechanical Support Considerations

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Role of LVAD

• Bridge to Transplantation
• Bridge to Better Devices
• Bridge to Restoration ??

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LVAD
Rose, REMATCH Group NEJM, 2001
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LVAD in CHF Class IV
LVAD
Medical Rx
Rose, REMATCH Group NEJM, 2001
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LVAD Post REMATCH Outcomes
Leitz, Circ.,2007 116 497-505
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LVAD implant
LVAD 8 months
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LVAD Impact

• Muscle
• Matrix
• Vessels

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Myocytes before and after LVAD insertion
Dilated Cardiomyopathy
Dilated CMP post LVAD
Donor Heart
(Yacoub, Europ Heart J 2001 22 534-40)
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End Diastolic Pressure / Volume Relationships

Normal
Post LVAD ( 4 mos.)
Pre LVAD
Mm Hg
Levin, 1996
Volume ml
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LVAD / Bridge to Restoration

• LVAD Implantation ( High Risk pts.)
• LV Restoration ( rebuilding timing ? )
• LVAD Removal ( collagen turnover,
  BNP, torsion)
• Long term results known

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Long term results
Ischemic
Non ischemic
( Site selected )
Hayama 2003
Suma, 2003
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Remote Muscle Status

• Ischemic ( normal or diffuse disease)
• Non Ischemic ( variable fibrosis)

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Cell Biology

• Macroscopic / Microscopic
• Relationship

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Diffuse Ischemic in Remote muscle
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Architectural Disadvantage

• Viable Remote muscle
• abnormal shape
• stretched non functioning area
• determine damage by gadolinium
• 
  or biopsy

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Wall Motion Improvement after CABG
Recovery
MRI hyper-enhancement
Gadolinium
Kim, NEJM, 2000
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Wall Motion Improvement after CABG
Recovery
( Restoration )
MRI hyper-enhancement
Gadolinium
Kim, NEJM, 2000
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Narrowing this Gap

• Explore Cell Engineering

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Cardiac Tissue Bioengineering

• Matrix ( Scaffolding)
• Cells ( myocyte, angiogenesis,
  fibroblasts, neural connections, etc)
• Growth

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The Cardiac Scaffold

• Macroscopic and Microscopic
• Marriage
• of
• Form and Function

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The Cardiac Scaffold

• Existing scaffold Ischemic region
• no vessels
• normal form
• Absent scaffold Dilated Ventricle
• 
  normal vessels
• 
  abnormal form

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Gadolinum Scan
Angina, no open LAD artery
De Oliviera, 2006
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Cell Implantation Only
preoperative
6 months
longitudinal
axial
De Olivera, 2006
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The Cardiac Scaffold

• Restoration Objective
• Create Scaffold
• Ischemic / non ischemic
• dilated cardiomyopathy
• Evaluate Remote Muscle

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Future of Successful Myoblasts

• Replace Transplant ?
• Replace Restoration?
• Add to restoration !!

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• 
  Unifying Conical Form
• Correct form ,
  not Disease
• Applicable in Dilated
  Cardiomyopathy
• Ischemic ( with and
  without scar)
• Valvular
• Non Ischemic

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• 
  Unifying Conical Form
• Correct form ,
  not Disease
• Bridge to Restoration
• Scaffold Creation / Cell Therapy
• Ischemic ( remote
  partial scar)
• Non ischemic (
  retained functional muscle)

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Prevailing AttitudesFuture

• Sulk Assault by catheter based
  technology
• Smile New pathways Innovated
• Surgical Restoration
• of CHF Geometry

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Restoration and the Helical Heart

• Commonality and Explanation
• How the otherwise absurd goal
• of universal understanding
  became thinkable
• 
  Leonardo Da Vinci
• by
  Kemp, 2004

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Purse-string suture and patch implantation
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Myocytes before and after LVAD insertion
Donor Heart
Dilated Cardiomyopathy
Dilated CMP post LVAD
(Yacoub, Europ Heart J 2001 22 534-40)
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SVR on Regional Circumferential Strain
Pre-surgery
7 days post-surgery
166 days post-surgery
Cirumferential strain from a single patient
PRE EARLY LATE EC-LAD 0.3 -4.4 -10.2 EC-RCA -6
.4 -1.4 -10.1 EC-LCx -12.6 -18.2 -16.1
courtesy of White, Cleveland Clinic
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Past
F. Robisczek M.D.
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Present
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Myocardial Strain
Bogaert, AJP, 2001
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Myocardial Strain
Bogaert, AJP, 2001
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Myocardial Strain / MRI fiber angulation
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SVR vs. Cardiac Transplant
(300 centers)
(14 pts)
Conte, 2007
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DENSE MRI
Wen ,NIH
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Cardiac Tagging(Deformation)
cine
tagging
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SVR Procedure
Pre - Rx
Post - Rx
cine
tagging
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PLV /
Cleveland Clinic
Franco-Cereceda A, et.al, JTCVS 2001121879-893
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Gadolinum Scan
Angina, no open LAD artery
De Oliviera, 2006
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preoperative 6 months
12 months
longitudinal
axial
De Olivera, 2006
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• 
  Unifying Conical Form
• Correct form ,
  not Disease
• Applicable in Dilated
  Cardiomyopathy
• Ischemic ( with and
  without scar)
• Valvular
• Non Ischemic
• Bridge to Restoration
• Scaffold Creation / Cell Therapy
• Ischemic ( remote
  partial scar)
• Non ischemic (
  retained functional muscle)