2008 napoli, congresso italo americano di cardiochirurgia, i dispositivi di contenimento nello scompenso cardiaco

1. Active and PassiveActive and Passive
Constraint DevicecsConstraint Devicecs
Stefano Nardi, MD, PhDStefano Nardi, MD, PhD
SANTA MARIA GENERAL HOSPITAL, TERNISANTA MARIA GENERAL HOSPITAL, TERNI
THORACIC SURGERY AND CARDIOVASCULAR DEPARTMENTTHORACIC SURGERY AND CARDIOVASCULAR DEPARTMENT
ARRHYTHMIA, EP CENTER AND CARDIAC PACING UNITARRHYTHMIA, EP CENTER AND CARDIAC PACING UNIT

2. ACHF:ACHF: Multistep, Therapeutic ApproachMultistep, Therapeutic Approach
Stage AStage A
At high risk, noAt high risk, no
structuralstructural
diseasedisease
Stage BStage B
Structural heartStructural heart
disease,disease,
asymptomaticasymptomatic
TherapyTherapy
TreatTreat
HypertensionHypertension
Treat lipidTreat lipid
disordersdisorders
Encourage regularEncourage regular
exerciseexercise
Discourage alcoholDiscourage alcohol
intakeintake
ACE inhibitionACE inhibition
TherapyTherapy
All measuresAll measures
under stage Aunder stage A
ACE inhibitorsACE inhibitors inin
appropriateappropriate
patientspatients
Beta-blockersBeta-blockers inin
appropriateappropriate
patientspatients
TherapyTherapy
All measuresAll measures
under stage Aunder stage A
Drugs:Drugs:
DiureticsDiuretics
ACE inhibitorsACE inhibitors
Beta-blockersBeta-blockers
DigitalisDigitalis
Stage CStage C
(NYHA I-II-III)(NYHA I-II-III)
Structural heartStructural heart
disease withdisease with
prior/currentprior/current
symptoms of HFsymptoms of HF
ElectricalElectrical
Therapy:Therapy:
CRT & ICDCRT & ICD
Stage DStage D
Refractory HFRefractory HF
requiringrequiring
specializedspecialized
interventionsinterventions
TherapyTherapy
All measuresAll measures
under stages A,B,under stages A,B,
and Cand C
MechanicalMechanical
assist devicesassist devices
HeartHeart
transplantationtransplantation
Continuous (notContinuous (not
intermittent) IVintermittent) IV
inotropic infusionsinotropic infusions
for palliationfor palliation
Hospice careHospice care

3. Background on Heart FailureBackground on Heart Failure
• One of the few major CV diseases rising in incidenceOne of the few major CV diseases rising in incidence
1
AHA. ’04; AHA ‘02. 2
Hunt SA, ACC/AHA guidelines ‘01
Population
Group Prevalence Incidence Mortality
Hospital
Discharges Cost
TotalTotal
populationpopulation
5,000,0005,000,000 550,000550,000
50%50%
within 5within 5
yearsyears
1,000,0001,000,000
$24.3$24.3
billionbillion
5 million people in US and 25 million people worldwide.
• More than 1 million pts hospitalized/yrMore than 1 million pts hospitalized/yr
• 12 million out-pt office visits12 million out-pt office visits
• HF-H one of largest expenses for CMSHF-H one of largest expenses for CMS1,21,2
• Mortality rates remain very highMortality rates remain very high

4. Heart Failure (CHF)Heart Failure (CHF)
Seeking answers, butSeeking answers, but
what about unanswerable questions?what about unanswerable questions?
 but many people (even somebut many people (even some
MD) do not realize whatMD) do not realize what
really needs to be done!really needs to be done!
• CHF is a very frightening term!CHF is a very frightening term!
• CHF is a very common medical problemCHF is a very common medical problem
• CHF can be successfully treatedCHF can be successfully treated

5. Heart Failure PathophysiologyHeart Failure Pathophysiology
Myocardial injury Fall in LV performance
Activation of RAAS, SNS, ET,
and others
Myocardial toxicity
Peripheral vasoconstriction
Hemodynamic alterations
Remodeling and
progressive
worsening of
LV function Heart failure symptomsMorbidity and mortality
ANP
BNP
Fonarow GC. Rev Cardiovasc Med. 2001;2:7-12.

6. Therapeutic GoalsTherapeutic Goals
• Relieve symptomsRelieve symptoms
• Reverse acute hemodynamic abnormalitiesReverse acute hemodynamic abnormalities
• Initiate treatments that will slow disease progression andInitiate treatments that will slow disease progression and
improve long-term survivalimprove long-term survival
• Apply treatment cost- effectivelyApply treatment cost- effectively
• Prevent end-organ dysfunctionPrevent end-organ dysfunction

7. Pharmacological ApproachPharmacological Approach
Digoxin,
Diuretics,
Idralazine
ACE-I
ß-blocker
and ACE-I
SOLVD
CONSENSUS
da -16 a -31% CIBIS II
COPERNICUS
- 35%
Mortality
CHF “fiveCHF “five––drug” Rxdrug” Rx
Class III-IV:Class III-IV:
40% Mortality/1 yr40% Mortality/1 yr
Class III-IV:Class III-IV:
80% Mortality/2yrs80% Mortality/2yrs
Class IV: 60%Class IV: 60%
Mortality/1 yrMortality/1 yr
Hunt, SA, et al ACC/AHA Guidelines for CHF, ‘01Hunt, SA, et al ACC/AHA Guidelines for CHF, ‘01

8. Growing interest for alternativeGrowing interest for alternative
procedures for advanced HF but…..procedures for advanced HF but…..
Risk of
alternative
procedure
Risk of
disease
progression
VSVS

9. Alternative OptionsAlternative Options
• Surgery is not often used to treatSurgery is not often used to treat
pts with CHFpts with CHF
• However, it can be a logical method of treatment inHowever, it can be a logical method of treatment in
cases in which traditional treatments are notcases in which traditional treatments are not
working for whatever reason.working for whatever reason.
• Then physicians seek to identify pts whoThen physicians seek to identify pts who
could have the greatest gain from surgicalcould have the greatest gain from surgical
intervention and with less risk.intervention and with less risk.
What about surgeryWhat about surgery??

10. The Unmet Need in HFThe Unmet Need in HF
• Despite OMT, HF remains a progressive disease that isDespite OMT, HF remains a progressive disease that is
accompanied by progressive LV remodelingaccompanied by progressive LV remodeling
• LV dilation produce a change in the morphology fromLV dilation produce a change in the morphology from
an ellipse to a more spherical shapean ellipse to a more spherical shape
• LV remodeling predicts mortality.LV remodeling predicts mortality.

11. Cardiac Support Devices (CSD)Cardiac Support Devices (CSD)
• MyosplintMyosplint
““SShapehape CChangehange TTherapy”herapy”
• Intracardiac struts.Intracardiac struts.
• May prevent further LV dilation, reduce wall stressMay prevent further LV dilation, reduce wall stress

12. Shape Change Rx (Myosplint)Shape Change Rx (Myosplint)

13. Passive Cardiac Diastolic Support
“Device-based on passive LV constraint
to treat DCM”. McCarthy, JTCS 2001
Objective:
counteract LV remodeling in IDC
 less invasive surgery (?)
 without remove myocardial tissue
Passive Constraint SupportPassive Constraint Support
Devices (PCSD)Devices (PCSD)

14. Passive Constraint SupportPassive Constraint Support
Devices (PCSD)Devices (PCSD)
 Provide LVEDD and LVEDV support to reduce
myocardial stretch
 Promote myocardial reverse remodeling
 Improve functional status
PCSD

15. How does PCSD work ?How does PCSD work ?
Increased
Myocyte Stretch
Increase
Wall Stress
Injury
Death
Ventricular
Remodeling
Decreased Cardiac Function
Heart Failure Symptoms
(NYHA Class, Hospitalizations)
Diastolic Wall Stress = Radius x Pressure
(Myocyte Stretch) Wall Thickness
Transmural Pressure =
LVEDP – CorCap Counter Pressure
Law of LAPLACELaw of LAPLACE

16. PCSD
Passive Constraint SupportPassive Constraint Support
Devices (PCSD)Devices (PCSD)

17. • Highly elastic compliant nitrol structureHighly elastic compliant nitrol structure
• Delivered with special delivery systemDelivered with special delivery system
(minitoracotomy)(minitoracotomy)
• Self-anchoring and self-tensioningSelf-anchoring and self-tensioning
• Pre sized (echo measurements)Pre sized (echo measurements)
• CRT/ICD compatibleCRT/ICD compatible
PCSDPCSD
ParacorParacor

18. PCSD ParacorPCSD Paracor

19. QoL and 6MWTQoL and 6MWT Threshold AnalysisThreshold Analysis
NYHA ClassNYHA Class Echo DataEcho Data
PCSD ParacorPCSD Paracor

20. Longitudinal
Load
(0.8 lbs/in)
Circumferential
Load
(0.8 lbs/in)
No Load
• New meshNew mesh
(multi-Filament Yarn / Knit(multi-Filament Yarn / Knit
Fabric)Fabric)
PCSD CorCapPCSD CorCap
– Optimal compliance - “stretchiness”Optimal compliance - “stretchiness”
– Bi-directional PropertiesBi-directional Properties
• Reshapes the heart to ellipsoidReshapes the heart to ellipsoid
– 31 micro fiber construction31 micro fiber construction
• Smooth fit on surface of heartSmooth fit on surface of heart
– Long term biocompatibilityLong term biocompatibility
• Reducing in MRReducing in MR
• No changes in dyastolicNo changes in dyastolic
properties of LVproperties of LV

21. PCSD CorCap
 n=148
91 received mitral valve repair
PCSD CorCap
 n=148
91 received mitral valve repair
Primary Endpoint:

Composite classification of improved, the same, or worse
based on occurrence of death, change in NYHA class, or
cardiac procedure indicative of HF progression
Primary Endpoint:

Composite classification of improved, the same, or worse
based on occurrence of death, change in NYHA class, or
cardiac procedure indicative of HF progression
ACORN TrialACORN Trial
AHA 2004
Control
n=152
102 received mitral valve repair
Control
n=152
102 received mitral valve repair
300 pts with Heart Failure
81.3% NYHA Class III, 3.7% Class IV
ischemic and non-ischemic pts, LVEF <30%, LVEDD >60 mm
55% male, mean age 52.5 years, with 6-MWT < 450 m
OMT (97% received ACE-I or ARB, 85% beta-blockers, 98% diuretic)
300 pts with Heart Failure
81.3% NYHA Class III, 3.7% Class IV
ischemic and non-ischemic pts, LVEF <30%, LVEDD >60 mm
55% male, mean age 52.5 years, with 6-MWT < 450 m
OMT (97% received ACE-I or ARB, 85% beta-blockers, 98% diuretic)
no CABG

22. Acorn Clinical Trial DesignAcorn Clinical Trial Design
300 Patients
Mitral Surgery Stratum
193 Patients
No Mitral Surgery Stratum
107 Patients
Control
MVR Alone
102 Patients
Treatment
MVR plus CSD
91 Patients
Control
OMT Alone
50 Patients
Treatment
OMT plus CSD
57 Patients
Median Follow-up of 23 mo.
504 patient years of Follow-up
(Randomized)(Randomized)
AHA 2004

23. Summary of PCSD effectsSummary of PCSD effects
ENDPOINTSENDPOINTS FavorsFavors p-valuep-value
Primary Clinical CompositePrimary Clinical Composite CSDCSD 0.020.02
SurvivalSurvival NeutralNeutral
Major Cardiac ProceduresMajor Cardiac Procedures CSDCSD 0.010.01
NYHANYHA CSDCSD 0.120.12
LVEDVLVEDV CSDCSD 0.0090.009
LVESVLVESV CSDCSD 0.0170.017
SphericitySphericity CSDCSD 0.0260.026
MLHFQMLHFQ CSDCSD 0.050.05
SF 36 (physical function)SF 36 (physical function) CSDCSD 0.0150.015
Re-HospitalizationsRe-Hospitalizations NeutralNeutral

24. Acorn Trial: SurvivalAcorn Trial: Survival
0
10
20
30
40
50
60
70
80
90
100
0 6 12 18 24
Months after Randomization
PercentSurvival
CSD Treatment (n=148)
Control (n=152)
p =
0.90
PCSD “Pushing the limits”PCSD “Pushing the limits”

25. Batista’s Operation:Batista’s Operation:
“Direct Surgical Therapy”“Direct Surgical Therapy”
• Excision of Lateral Wall with a linear closureExcision of Lateral Wall with a linear closure
• Reduction of LVEDV, LVESV and wall stressReduction of LVEDV, LVESV and wall stress
(Laplace’s law).(Laplace’s law).• High initial enthusiasmHigh initial enthusiasm (between ‘96 and ’00, 58 papers and editorials describe first experiences)(between ‘96 and ’00, 58 papers and editorials describe first experiences)

26. WallThickness[%]020406080100
MidventricularFiberStress
@End-Diastole[kPa]
02468101222.5%
25.1%
WallThickness[%]020406080100
MidventricularFiberStress
@End-Systole[kPa]
010203040506070
DCM10%LateralResection20%LateralResection
28.3%
29.3%
WallThickness[%]020406080100
MidventricularFiberStress
@End-Systole[kPa]
010203040506070
DCM10%LateralResection20%LateralResection
P-V RelationshipsP-V Relationships
Change in
Systolic
Elastance
Change in
Diastolic
Compliance
Batista Procedure

27. DCM
10%
Lateral Resection
20%
Lateral Resection
01020304050
StrokeVolume[ml]EF[%]1. Ratcliffe, JTCVS ‘98
LVEF is not enough1
• SD: 46% of the DeathsSD: 46% of the Deaths
• CHF/Shock: 13%,CHF/Shock: 13%,
• Sepsis: 6%,Sepsis: 6%,
• Emergency LVAD: 20%Emergency LVAD: 20%
• No SD in Survival with OMTNo SD in Survival with OMT
Improvement in Symptoms,Improvement in Symptoms,
NOT SurvivalNOT Survival

28. INACTIVE
AREA
Excitabile Gap
Arrhythmic Death

29. • The twisting ability of LV is reduced
with reduction of LVEF and filling.
• As CHF progresses, the LV dilation
often change both SIZE and SHAPE
that becomes more spherical
• MV apparatus goes out of proper
anatomical alignment, with
reduction to assist LV in the
contraction MR (MR) – work-load
• The distortion of LV shape
reduces the force vector that moves
away from AoV, resulting in
inefficient pumping and turbulence in
LV
Consideration

30. Left Ventricular Remodelling
Necrosis M.I.
Normal
Infarctus
Expansion
Cicatrisation Slimming Dilatation
Hypertrophy of
sound myocardium
(Compensation)
L.V. global
Dilatation
Progressive
deterioration
L.V. RESPONSE and
REMODELING

31. “SVR – Dor procedure”
(GOALS)
• Reconstruct a new apex
• Reduce the ventricle to an optimal volume
• Restore the ventricle to an elliptical shape
• Reorient the papillary muscles and muscle fibers

32. • The akinetic segments are excluded behind a Dacron
patch, even if the muscle appears grossly normal.
• The very stiff patch is further reinforced by folding
the residual myocardium on top of it, resulting in a
dual layer patch.
Before After
Reduced Twist
“Spherical”
Full Twist
“Bullet”
Surgical Ventricular Restoration
DOR procedure

33. Restore TrialRestore Trial
thethe RReconstructiveeconstructive EEndoventricularndoventricular SSurgery returningurgery returning
TTorsionorsion OOriginalriginal RRadiusadius EElliptical shapelliptical shape
(~2000 pts from ’98 to ’03, 12 centres worldwide)(~2000 pts from ’98 to ’03, 12 centres worldwide)
Athanasuleus CL, JACC. ‘04
• MI in anteroseptal portion of LV
• Enlarged LV
• ESV index > 50ml/m2
• EDV index of > 110 ml/m2
• Large area of Akinesis or Dyskinesis
• Asynergy >30% of circumference or 3/10 Echo
anterior segment  STICH Trial
• Acceptable EF of basal portion and lateral wall
• Good RV function
• Candidate for CABG

34. Schreuder, J Th C Srg ‘05
EFFECTS on STRESS
Restore TrialRestore Trial
RESULTSRESULTS
Athanasuleus CL et al. JACC ‘04

35. Restore TrialRestore Trial
SURVIVALSURVIVAL
NYHA Class EF %
Morphology ESVI ml/m2
Athanasuleus CL et al. JACC ‘04

36.  In Hospital MortalityIn Hospital Mortality <8%<8%
 1 Year Freedom from HF1 Year Freedom from HF 80%80%
Restore TrialRestore Trial
RESULTSRESULTS
Overall five-year survival
Athanasuleus CL et al. JACC ‘04

37. “SVR – DOR procedure”
CONSIDERATIONS
(Dor, Thoracic and CV, Vol.01)
• The ability to properly reshape could be a Challenge
• When surgically RE-SIZING and RE-SHAPING LV,
it’s crucial to estimate the final LV morphology and
volume, as well as the orientation of PAPILLARY
MUSCLES and AORTIC PLANE
• Making a too small LV it will lead to Pulmonary
Hypertension, whereas a too large LV leave the pt’s
heart in a state to it’s pre-operative condition

38. • In ‘01 was described a new technique
using an Endoventricular Shaper
• The Shaper is inflated to a volume
based on the pts BSA and EDV
“Surgical Anterior Ventricular Endocardial
Restoration - SAVER”
(TR3
ISVR procedure)
• Re-sizing the ventricle around a
shaper inflated ensures that a too
small/large LV will not be created.
• SVR using a specific Shaper is able to
reduce proportionally both short and
long axis (only long-axis create a
spherical LV and lead MR)
• Shaper defines the new apex.

39. • LV in incised in the akinetic
tissue area and inspect for TR
and for the border zone
(akinetic and viable muscle)
feeling for thin tissue or by
visually identifying necrotic
tissue.
• A SHAPER is inserted in the
LV with the basal portion
seated against the AoV and MV
annuluses, and the tip that
identifies the new LV apex
location.
TR³ISVR
Technical procedure

40. TR3
ISVR PROCEDURE
BEFORE AFTER

41. HEART FAILURE & CaHEART FAILURE & Ca++++
1. Beuckelmann DJ, Basic Res Cardiol ‘’97; 2. Gomez AM, Science ‘’97
The weakened contractility of failing cardiac myocytes isThe weakened contractility of failing cardiac myocytes is
believed to result, in large part, from anbelieved to result, in large part, from an abnormally lowabnormally low
amount of Caamount of Ca++++
delivered to the myofilaments during eachdelivered to the myofilaments during each
beat, independent of disease etiology.beat, independent of disease etiology.1,21,2
Φ2 – Plateau
(absolute refractory)
K+
Ca++
3) Slower, inward Ca++
channels open, matching outward K+
and maintaining the membrane near 0 mV (Φ2 – Plateau)

42. Action Potential, Ca++ andAction Potential, Ca++ and
ContractilityContractility
1.1. Reduction in the amplitude and increase in durationReduction in the amplitude and increase in duration
of APof AP
ControlControl Heart FailureHeart Failure
AP (EAP (Emm))
[Ca[Ca2+2+
]]ii
ContractionContraction
2.2. Reduction in the upslope and downslop of the CaReduction in the upslope and downslop of the Ca++++
transienttransient
3. Parallel reduction in the upslope and downslop of the
peak developed tension

43. CaCa2+2+
flux in the Heartflux in the Heart

44. • NEC are able to prologed the AP duration due to
enhanced trans-sarcolemmal Ca++
entry
• Ryanodine is able to block Ca++
relase from the SR,
then decrease the effects of NEC; SR is full loading
with Ca++
(major contributor)
Experimental Finding
Subthreshold pacing for HFSubthreshold pacing for HF
Transmembran
ePotential(mV)
Time (ms)
100 200 300 400 500
Phase 2
Phase 1
Phase 3
Phase 4
-50
0
50
-100
Phase0
Threshold Critical phase of APCritical phase of AP
for the modulationfor the modulation
of the E-C couplingof the E-C coupling
RV1
RV
2
RA

45. Heart FailureHeart Failure
CCM – The ConceptCCM – The Concept
1- Detect local
activation
2- Apply
NEC signal
NEC

46. Tension(%max.)
50
100
Length (%∆)
Starling Law
1.5 2 2.5 µ
CCM
Increased tension
Increased
contractility
Increased
Pressure
Remote Recruitment
Heart FailureHeart Failure
CCM – Mechanisms in HumanCCM – Mechanisms in Human

47. CCM effectsCCM effects
CCM artifact
Immediate return
to baseline
NO QT variation
LVP(mmHg)
LVV ( ml)
Segment Lengt h ( mm)
0
60 8070 60 8 07 0 60 8 070
15
24
1 6 17 18
2 5 26 2 7 24 25 2 6 27 2 4 25 26 27
1 20
60
LVP(mmHg)
0
1 20
60
LVV ( ml)LVV ( ml)
15 16 1 7 18 15 16 17 1 8
Ant e rio r CCM Post e rior CCM Combine d CCM
Segment Lengt h ( mm) Segment Length ( mm) Segment Length ( mm)
0
1 20
60
Segment Length ( mm) Segment Length ( mm)
LVP(mmHg)
AnteriorRegionPosteriorRegion

48. LVP
[mmHg]
ECG
dP/dt
Dp/Dt improvement 8.7% 5’ after CCM (Millar™ in LV)
CCM
Dp/DtDp/Dt
at IMPLANTat IMPLANT

49. CCM – Acute LV ResultsCCM – Acute LV Results
artifact
no change in QTc durationno change in QTc duration
RV1
RV
2
RA

50. Basal Active signal
ECHO Color KinesisECHO Color Kinesis

51. Heart FailureHeart Failure
CCM & CRT - ResultsCCM & CRT - Results

52. Heart FailureHeart Failure
CCM – Chronic ResultsCCM – Chronic Results
Left Ventricular Ejection Fraction
0
10
20
30
40
50
60
70
80
Baseline 3-hour Phase 7-hour Phase
Study Phase
Percent
Peak VO2
10
12
14
16
18
20
22
Baseline 3-hour Phase 7-hour Phase
Study Phase
ml/kgofbodyweight/min
mRNA Expression for ANP
mRNA Expression for BNP
mRNA Expression of b1-Adrenergic Receptor
mRNA Expression of SERCA-2a
NL HF-Sham HF + CCMNL HF-Sham HF + CCM
mRNA Expression for aMHC
b1-AR
ANP
BNP
aMHC
Serca-2a

53. Therapies for Heart FailureTherapies for Heart Failure
• Natriuretic peptidesNatriuretic peptides
• Endothelin antagonistsEndothelin antagonists
• VasopeptidaseVasopeptidase
inhibitorsinhibitors
• Cytokine antagonistsCytokine antagonists
• StatinsStatins
• ErythropoietinErythropoietin
• External enhanced counterExternal enhanced counter
pulsationpulsation
• Cardiac resynchronizationCardiac resynchronization
therapy (CRT)therapy (CRT)
• Routine use of ImplantableRoutine use of Implantable
Cardiac Defibrillators (ICD)Cardiac Defibrillators (ICD)
• Ventricular constraintVentricular constraint
devices (VCD)devices (VCD)
• Cell transplantationCell transplantation
• Total artificial heart /Total artificial heart /
permanent LVADspermanent LVADs
ConclusionsConclusions

54. Advanced HFAdvanced HF
ConclusionsConclusions
• Alternative Therapeutic Options could be a logical method ofAlternative Therapeutic Options could be a logical method of
treatment in cases in which traditional approaches are not workingtreatment in cases in which traditional approaches are not working
(for whatever reason).(for whatever reason).
• Then it’s crucial to identify the right approach ableThen it’s crucial to identify the right approach able
to give us the greatest to gain from specificto give us the greatest to gain from specific
intervention with less risk.intervention with less risk.

55. Not all limitations are yet well defined, multicentric trials
are ongoing (and are mandatory!) to:
 optimize patients selection
optimize specific (surgical) techniques
Cardiac Support Devices are an alternative
option and is still developing
Always Available
Some of them satisfying short and mid-term results
Advanced HFAdvanced HF
ConclusionsConclusions

56. DownhillDownhill
IrreversibleIrreversible
High risk for SCDHigh risk for SCD
ProgressiveProgressive
Natural History of CHFNatural History of CHF
EchoEcho

57. My Biased ViewpointMy Biased Viewpoint
• The “natural history” of CHF does notThe “natural history” of CHF does not
exist and is changing.exist and is changing.
• CHF could be reversibleCHF could be reversible
• CHF could be preventableCHF could be preventable
The Challenge……….The Challenge……….

58. The Challenge……….The Challenge……….
Remember that Nature has his
own limits…..
Giving every single patient:
•the right therapy (only one is enough??)
•at the right time (different specialists in
different moments of the same disease)

59. Thank you for yourThank you for your
attentionattention
EchoEcho
The physicianThe physician
TheThe
sonographersonographer
The surgeronThe surgeron
Multidisciplinary Approach!!Multidisciplinary Approach!!

60. BACK-UPBACK-UP

61. Therapies for Advanced HFTherapies for Advanced HF
• ANP, BNPANP, BNP
• Endothelin antagonistsEndothelin antagonists
• Vasopeptidase-IVasopeptidase-I
• Cytokine antagonistsCytokine antagonists
• StatinsStatins
• ErythropoeitinErythropoeitin
• IABPIABP
• CRT/ICDCRT/ICD
• Cardiac SupportCardiac Support
Devices (CSD)Devices (CSD)
• Cell transplantationCell transplantation
• Total artificial Heart/Total artificial Heart/
permanent LVADpermanent LVAD

62. Low dose LV CCMLow dose LV CCM
incorporated into standardincorporated into standard
CRT deviceCRT device
Multisite LV CCMMultisite LV CCM
The next FUTUREThe next FUTURE

63. ConclusionsConclusions
 Regarding the resultsRegarding the results HTxHTx still remains the goldstill remains the gold
standard treatment for Advanced heart failurestandard treatment for Advanced heart failure
 Alternative surgery limitations are not yet well defined:
multicentric trial are ongoing (and are mandatory!) to:
 optimize patients selection
 optimize surgical techniques
Alternative surgery is an effective option and is
still developing
No waiting list (whenever we like)
Always Available
Satisfying mid-term results

64. The Challenge……….The Challenge……….
•Multidisciplinary Approach!!Multidisciplinary Approach!!
Remember that Nature has his
own limits…..
Giving every single patient:
•the right therapy (only one is enough??)
•at the right time (different specialists in
different moments of the same disease)

65. Pharmacological, ModulationPharmacological, Modulation
of Cardiac Contractilityof Cardiac Contractility
•PDE inhibitor
•β-adrenergic agonist
•digitalis
•Benefits on hemodynamics and symptoms
•Neutral/negative effects on mortality
•Only digitalis on a chronic basis (selected pts)

66. Burkhoff D, Am J Phys ‘87
CANINE modelCANINE model
What does it mean CHF ?What does it mean CHF ?VO2(ml/min/mVO2(ml/min/m22
))
DODO22 (ml/min/m(ml/min/m22
))
Critical DOCritical DO22
DISOXIADISOXIA
Critical VOCritical VO22
NormalNormal

67. Spragg DD, Circulation ’03
Regional Alterations of Protein
Expression in CHF dogs

68. Mesenchymal Stem Cells forMesenchymal Stem Cells for
Cardiac RegenerationCardiac Regeneration
Images courtesy of Dara L. Kraitchman, V.M.D., Ph.D.
• Injection of small volumes of material can change cardiac
mechanicistict properties with border zone placement the most
likely to reduce pathological wall stresses.

69. COLOR KINESIS
SYSTOLIC FUNCTION
Remote effectRemote effect

70. Matrix-Assisted MyocardialMatrix-Assisted Myocardial
Stabilization (LVEF Model Simulation)Stabilization (LVEF Model Simulation)

71. Effect onEffect on
LV Pressure-Volume RelationshipsLV Pressure-Volume Relationships

72. Effect on Ejection FractionEffect on Ejection Fraction

73. The Optimizer™ IIIThe Optimizer™ III rechargable devicerechargable device
RV1
RV2
RA

74. PatientPatient
ClassificationClassification
Any One OfAny One Of
SameSame
NYHANYHA
ImprovedImproved
NYHANYHADeathDeath MCPMCP(1)(1)
WorsenedWorsened
NYHANYHA
WorsenedWorsened   
UnchangedUnchanged 
ImprovedImproved 
(1)
Adjudicated Major Cardiac Procedures indicative of HF Progression: Transplant,
LVAD, CABG, BiV Pacing, and MV surgery (repeat)
• Pts functional status after a minimum of 12 mo FU
Acorn Clinical Trial DesignAcorn Clinical Trial Design
composite primary end-pointcomposite primary end-point

75. BVP & BVP+CCMBVP & BVP+CCM
Sinergistic Effects

76. Therapeutic GoalsTherapeutic Goals
• Relieve symptomsRelieve symptoms
1. Fonarow GC. Rev Cardiovasc Med. 2002;3(suppl 4):S18–S27.
2. Stier CT Jr et al. Cardiol Rev. 2002;10:97–107.
3. Masai T et al. Ann Thorac Surg. 2002;73:549–555.
• Reverse acute hemodynamic abnormalitiesReverse acute hemodynamic abnormalities
• Initiate treatments that will slow disease progression andInitiate treatments that will slow disease progression and
improve long-term survivalimprove long-term survival
• Apply treatment cost- effectivelyApply treatment cost- effectively
• Prevent end-organ dysfunctionPrevent end-organ dysfunction

77. • Reduce dyspnea and other signs and symptomsReduce dyspnea and other signs and symptoms
of CHFof CHF
End PointsEnd Points
• Lower PCWP with adequate systemic perfusionLower PCWP with adequate systemic perfusion
• Use of ACE-I, aldosterone antagonists and β-Use of ACE-I, aldosterone antagonists and β-
blockers before hospital dischargeblockers before hospital discharge
• Shorten length of stay, minimize use of ICU,Shorten length of stay, minimize use of ICU,
reduce readmissionsreduce readmissions
• Inhibit RAA systemInhibit RAA system
• Monitor inflammation caused by infectionMonitor inflammation caused by infection
following a major surgery or traumafollowing a major surgery or trauma

78. Prolate SpheroidalProlate Spheroidal
CoordinatesCoordinates
Costa, Biomech Eng. ‘96
www.continuity.ucsd.edu
Ventricular MuscleVentricular Muscle
Fiber OrientationFiber Orientation
Walker et al, J Thorac CV Surg. ‘05
CHF PATHOLOGY

79. Definition of StressDefinition of Stress
Fung, A 1° Course in Continuum Mechanics, ‘94
LV PV loopsLV PV loops
McCulloch, Theory of Heart, ‘91
CHF PATHOLOGY

80. Model ofModel of
ShorteningShortening
DeactivationDeactivation
Guccione and McCulloch, J
Biomech Eng. ‘93 Feb;115(1):72-90
Muscle ContractionMuscle Contraction
Model ComparisonModel Comparison

81. • Non-conventional Surgical RxNon-conventional Surgical Rx
• Dedicated procedures and devicesDedicated procedures and devices
Surgical Reverse
Remodeling
• Passive Diastolic Support
• Dynamic Cardiomioplasty
• “Batista” procedure
• Undersized Mitral Annuloplasty
• Ventriculoplasty
• Mechanical circulatory assistance
Alternative and aggrssive RxAlternative and aggrssive Rx
for advanced Heart Failurefor advanced Heart Failure

82. Specific Interventions
• Partial Left Ventriculectomy
(J Thorac Cardiovasc Surg. 2001 Sep;122(3):592-9)
• Myocor Myosplint
(Ann Thorac Surg, 0’03 Oct;76(4):1171-80; discussion
1180)
• Surgical Anterior Ventricular Restoration (Ann
Thorac Surg. 2005 Jan;79(1):185-93)
• Matrix-Assisted Myocardial Stabilization
(Circulation. 2006)

83.  3+/4+3+/4+ MRMR due to annulus dilatationdue to annulus dilatation
 No morphologic/structural valve alterationsNo morphologic/structural valve alterations
Functional Mitral RegurgitationFunctional Mitral Regurgitation
 NYHA class III-IV with OMTNYHA class III-IV with OMT
 E.F.E.F. <<35 %35 %
 LV VTDiLV VTDi >>110 ml110 ml

84. Surgical Indication in well selected pts
• not favourable age for HTx.
• signs e symptoms of pulmonary congestion
(congestive/backward HF) more than decreased
antegrade perfusion (forward HF)
Functional Mitral Regurgitation
Undersized Mitral Annuloplasty

85. • Secondary MR affects up to 60% of CHF pts
• Normal MV function requres maintenance of
chordal, annular, subvalvular, and valvular relationships
• Any etiolgy annular
Mitral RegurgitationMitral Regurgitation

86. Non-ischemic MR: due to annular dilation, papillary muscle
displacement, loss of leaflet coaptation due to tethering,
Mitral Valve RepairMitral Valve Repair

87. Mitral Valve RepairMitral Valve Repair
• Ischemic MR: due to annular dilation, papillary muscle displacement,
loss of leaflet coaptation due to tethering, $plus papillary muscle

88. • Dyspnea and other signs andDyspnea and other signs and
symptoms of heart failuresymptoms of heart failure11
Therapeutic Goals for ADHFTherapeutic Goals for ADHF
• Relieve symptomsRelieve symptoms
Goals End Points
1. Fonarow GC. Rev Cardiovasc Med. 2002;3(suppl 4):S18–S27.
2. Stier CT Jr et al. Cardiol Rev. 2002;10:97–107.
3. Masai T et al. Ann Thorac Surg. 2002;73:549–555.
• Reverse acuteReverse acute
hemodynamichemodynamic
abnormalitiesabnormalities
• Initiate treatments that will slowInitiate treatments that will slow
disease progression and improvedisease progression and improve
long-term survivallong-term survival
• Apply treatment cost-Apply treatment cost-
effectivelyeffectively
• Prevent end-organPrevent end-organ
dysfunctiondysfunction
• Lower PCWP with adequateLower PCWP with adequate
systemic perfusion1systemic perfusion1
• Use of ACE-I, aldosteroneUse of ACE-I, aldosterone
antagonists and β-blockersantagonists and β-blockers
before hospital discharge1before hospital discharge1• Shorten length of stay,Shorten length of stay,
minimize use of ICU, reduceminimize use of ICU, reduce
readmissions1readmissions1
• Inhibit RAA systemInhibit RAA system
• Monitor inflammationMonitor inflammation
caused by infectioncaused by infection
following a major surgeryfollowing a major surgery
or trauma2,3or trauma2,3

89. NEJM ‘05-352NEJM ‘05-352
CRTCRT
Class III-IV:Class III-IV: 40% Mortality @ 1 Year40% Mortality @ 1 Year
Class III-IV:Class III-IV: 80% Mortality @ 2 Years80% Mortality @ 2 Years
Class IV: 60%Class IV: 60% Mortality @ 1 YearMortality @ 1 Year

90. Advanced HeartAdvanced Heart
FailureFailure Options ?Options ?
Stage DStage D
Refractory HFRefractory HF
requiringrequiring
specializedspecialized
interventionsinterventions
TherapyTherapy
All measuresAll measures
under stages A,B,under stages A,B,
and Cand C
MechanicalMechanical
assist devicesassist devices
HeartHeart
transplantationtransplantation
Continuous (notContinuous (not
intermittent) IVintermittent) IV
inotropic infusionsinotropic infusions
for palliationfor palliation
Hospice careHospice care
Hunt, SA, et al ACC/AHA Guidelines for CHF, ‘01Hunt, SA, et al ACC/AHA Guidelines for CHF, ‘01

92. Mortalità
totale
Frazione di
eiezione
Morte per
causa aritmica
PEA
Challenges in management of CHF
NYHA II
Other
24%
CHF
12%
Sudden
death
64%
N=103
NYHA III
Sudden
death
59%
CHF
26%
Other
15%
N=232
NYHA IV
Sudden
death
33%
CHF
56%
Other
11%
N=27 MERIT-HF

94. Effects of CSDEffects of CSD
Cell Structure and FunctionCell Structure and Function
NL CSDHF
Cell-Stretch Response Protein
NL CSDHF
CSDHFNL
p21ras
c-fos
p38 α/β
MAPK
Saavedra WF, JACC ‘02; Sabbah HN, Circ Res 03
Cardiomyocyte Hypertrophy
*
*#
50
75
100
125
150
175
200
225
10
15
20
25
30
35
40
5
6
7
8
9
10
11
12
HF CSDNLHF CSDNL HF CSDNL
MCSA (µm
2
) Length (µm) Width (µm)
* * *
x102
** **
**
Cardiomyocyte Apoptosis (per 1000)
*
*#
0.0
0.1
0.2
0.3
0.4
0.5
0
1
2
3
4
5
6
7
0.0
0.5
1.0
1.5
2.0
2.5
3.0
3.5
4.0
HF CSDNLHF CSDNL HF CSDNL
Overall Remote Border
*
*
*

95. NYHA ClassNYHA Class Echo DataEcho Data
ParacorParacor
Ventricular Support SystemVentricular Support System

96. Natural History of DCMNatural History of DCM
1 yr Mortality
ITALIAN NETWORK CHF
0
10
20
30
40
50
4,1 %4,1 %
11,7 %11,7 %
24,8 %24,8 %
36,7 %36,7 %
15,1 %15,1 %
(%)(%)
NYHA I
1
NYHA II
2,14
[1,33-3,44]
NYHA III
3,77
[2,32-6,12]
NYHA IV
5,54
[3,23-9,48]
Total
Relative
Risk

97. ResultResult

98. ““DDirectirect SSurgicalurgical TTherapyherapy””
Partial Left Ventriculectomy or BatistaPartial Left Ventriculectomy or Batista
procedureprocedure
“Surgical Anterior Ventricular Endocardial
Restoration - SAVER”
(Dor and TR3
ISVR procedure)
Management of AdvancedManagement of Advanced
CHFCHF

100. INACTIV
E AREA
EletricallyEletrically
inactive areainactive area
Excitabile Gap

101. Myocor MyosplintMyocor Myosplint
ConclusionsConclusions
• Reduction in diastolic fiber stress was approx.Reduction in diastolic fiber stress was approx.
similar to Batista.similar to Batista.
• Balanced shift of end-diastolic compliance andBalanced shift of end-diastolic compliance and
end-systolic elastance.end-systolic elastance.
• As a result, there was an improvement inAs a result, there was an improvement in
Starling’s law that was related to the amount ofStarling’s law that was related to the amount of
Myosplint tension.Myosplint tension.

102. Partial Left VentriculectomyPartial Left Ventriculectomy
(Batista)(Batista)
ConclusionsConclusions
• LV wall Stress was reduced by approx. 25%LV wall Stress was reduced by approx. 25%
• Shift in end-diastolic compliance was greaterShift in end-diastolic compliance was greater
than the reduction in end-systolic elastance.than the reduction in end-systolic elastance.
• As a result there was a reduction in CO andAs a result there was a reduction in CO and
decrement in Starling’s law.decrement in Starling’s law.
• LVEF was not a good measure of LV function.LVEF was not a good measure of LV function.

103. Normal Papillary
Muscle Angle
30°-40°
Orientation of
CHF pt 60-80°
• As CHF progresses, the
associated dilation of the
LV will often pull the MV
apparatus out of proper
anatomical alignment (MR)
• The misalignment also
reduces the ability of MV
apparatus to assist in the
contraction of the LV.
• This is additional work to
these muscles.
Left Ventricular Remodelling
Mitral Valve

104. Normal Papillary
Muscle Angle
30°-40°
Orientation of
CHF pt 60-80°
• As CHF progresses, the
associated dilation of the
LV will often pull the MV
apparatus out of proper
anatomical alignment (MR)
• The misalignment also
reduces the ability of MV
apparatus to assist in the
contraction of the LV.
• This is additional work to
these muscles.
Left Ventricular Remodelling
Mitral Valve

105. (Dor, Thoracic and CV, Vol.01)
• Making a too small LV it will
lead to immediate Pulmonary
Hypertension
• Making a too large LV leaves
the pt’s heart in a state
similar to its pre-operative
condition
“SVR – DOR procedure”
Limitations
• The Surgeron’s ability is to
achieve a correct size (3-D)

106. (Dor, Thoracic and CV, Vol.01)
“SVR – DOR procedure”
Limitations

107. • The Fontan suture, or purse string,
is started at the new apex point and
the suture continues along the
border of the akinetic zone and the
intersection of the Shaper.
• After the Fontan stitch is in place
and the LV tightened around the
Shaper, the patch is sutured into
the LV on the rim created by the
Fontan stitch.
TR³ISVR
Technical procedure

108. • AMI in antero septal portion of the LV.
• Enlarged LV between 100-180 ml/m2, EDVI
• Asynergy of > 35%
• Good lateral wall motion
• Good basal portion of the ventricle
• Good contraction
• Good RV
TR3
ISVR PROCEDURE
IDEAL PATIENT

109. Contraindications
• Pulmonary pressure >
60mmHg with MR
• Asynergy of >60%
• Asynergy of <35%
• LV volume > 180 ml/m2
TR3
ISVR PROCEDURE
•
A failing right ventricle
demonstrated as a low
right ventricle EF or TAPS
(Tricuspid Annular Plane
Systolic Movement) less
than 13mm•
Infarcts in two distinct
areas of the ventricle
•
Pulmonary pressure >
60mmHg without MR
RELATIVEABSOLUTE
These CI do not rule out
every pt, but alert you to the
fact that they are at greater
risk and need to be closely
evaluated before being
recommended for surgery

110. Cardiac ContractilityCardiac Contractility
MODULATIONMODULATION
(Non Exitatory Current)(Non Exitatory Current)
Subthreshold PacingSubthreshold Pacing
for Advanced Heartfor Advanced Heart
FailureFailure

111. 1
Will CCM modify contractileWill CCM modify contractile
function of segments remotefunction of segments remote
from the electrode?from the electrode?
How wide is the area whereHow wide is the area where
contractility enhancement can becontractility enhancement can be
obtained?obtained?2

112. CCM
No impairment in diastolic functionNo impairment in diastolic function
COLOR KINESIS
DIASTOLIC FUNCTION

113. mRNA Expression for ANP
mRNA Expression for BNP
mRNA Expression of b1-Adrenergic Receptor
mRNA Expression of SERCA-2a
NL HF-Sham HF + CCMNL HF-Sham HF + CCM
mRNA Expression for aMHC
b1-AR
ANP
BNP
aMHC
Serca-2a
Unpublishdd dataUnpublishdd data
Heart FailureHeart Failure
CCM – Mechanisms in HumanCCM – Mechanisms in Human

114. Baseline LV-CCMLV-CCM RV-CCMRV-CCM CCM plus CRTCCM plus CRT
Heart FailureHeart Failure
CCM – Acute ResultsCCM – Acute Results

115. LVP(mmHg)
LVV ( ml)
Segment Lengt h ( mm)
0
6 0 8070 60 8 07 0 60 8070
1 5
24
16 1 7 18
25 26 27 24 25 2 6 27 24 25 2 6 27
1 20
60
LVP(mmHg)
0
1 20
60
LVV ( ml)LVV ( ml)
15 16 1 7 1 8 15 16 17 1 8
Ante rio r CCM Post e rior CCM Combine d CCM
Segment Lengt h ( mm) Segment Length ( mm) Segment Lengt h ( mm)
0
1 20
60
Segment Length ( mm) Segment Lengt h ( mm)
LVP(mmHg)
AnteriorRegionPosteriorRegionACUTE EFFECTS ON DOGSACUTE EFFECTS ON DOGS

116. Heart FailureHeart Failure
CCM – Chronic ResultsCCM – Chronic Results

117. ““PPassiveassive CConstraintonstraint DDevices”evices” (PCD)(PCD)
(CorCap, Paracor)(CorCap, Paracor)
““DDirectirect SSurgicalurgical TTherapyherapy” (DST)” (DST)
Partial Left Ventriculectomy (Batista procedure)Partial Left Ventriculectomy (Batista procedure)
“Surgical Anterior Ventricular Endocardial
Restoration - SAVER”
(Dor and TR3
ISVR procedure)
““SShapehape CChangehange TTherapyherapy” (SCT)” (SCT)
(Myosplint)(Myosplint)
Cardiac Constraint Support (CCS)Cardiac Constraint Support (CCS)

118. a Vicious Cyclea Vicious Cycle
Abnormal RV-
LV sequence
Mitral Regurgitation
Segmental
Dyskinesia
Dysynchronous Contraction
Abnormal LV
activation
sequence
↑ Neurohormones
↓ LVEF
Dissynchrony
RV/LV
filling flow

119. Surgery for HFSurgery for HF (Batista)(Batista)
“Direct Surgical Therapy”“Direct Surgical Therapy”
Excision of
lateral wall
Linear
closure
DCM Model

120. DCM
10%
Lateral Resection
20%
Lateral Resection
01020304050
StrokeVolume[ml]EF[%]1. Dickstein, 113:1032 - ‘97
2. Ratcliffe, JTCVS 116:566 - ‘98
LVEF is not enough1,2
Batista Procedure
• LV wall Stress was reduced ~LV wall Stress was reduced ~
25%25%
• Shift in LVED compliance wasShift in LVED compliance was
greater than the reduction ingreater than the reduction in
LVED elastance.LVED elastance.
• As a result, CO was reduce andAs a result, CO was reduce and
Starling’s law decrementStarling’s law decrement

121. Improvement in Symptoms,Improvement in Symptoms,
NOT SurvivalNOT Survival
• Sudden Death:Sudden Death:
46% of the Deaths46% of the Deaths
• CHF/Shock: 13%,CHF/Shock: 13%,
• Sepsis: 6%,Sepsis: 6%,
• Emergency LVAD: 20%Emergency LVAD: 20%
• No Difference in SurvivalNo Difference in Survival
Compared to OMTCompared to OMT
Batista Procedure

122. First the surgeon palpates to determine
the border of the akinetic region.
A patch is sutured at that border
And the residual myocardium is folded over itself
resulting in a thicker double-layer patch.
Surgical Anterior Ventricular
Endocardial Restoration (SAVER)

123. New Therapies for Heart FailureNew Therapies for Heart Failure
• Natriuretic peptidesNatriuretic peptides
• Endothelin antagonistsEndothelin antagonists
• VasopeptidaseVasopeptidase
inhibitorsinhibitors
• Cytokine antagonistsCytokine antagonists
• StatinsStatins
• ErythropoeitinErythropoeitin
• External enhanced counterExternal enhanced counter
pulsationpulsation
• Cardiac resynchronizationCardiac resynchronization
therapytherapy
• Routine use of ImplantableRoutine use of Implantable
Cardiac Defibrillators (ICD)Cardiac Defibrillators (ICD)
• Ventricular constraintVentricular constraint
devicesdevices
• Cell transplantationCell transplantation
• Total artificial heart /Total artificial heart /
permanent LVADspermanent LVADs

124. • LV dilation produce aLV dilation produce a
change in the morphologychange in the morphology
from an ellipse to a morefrom an ellipse to a more
spherical shapespherical shape
The Unmet Need in HFThe Unmet Need in HF
• LV remodeling predicts mortality.LV remodeling predicts mortality.
• Despite OMT, HF remains a progressiveDespite OMT, HF remains a progressive
disease that is accompanied bydisease that is accompanied by
progressive LV remodelingprogressive LV remodeling

125. TOTAL
Mortality
Ejection
Fraction
Death for
Arrhythmic
Causes
PEA
Batista Procedure
Arrhythmic Death
NYHA II
Other
24%
CHF
12%
Sudden
death
64%
N=103
NYHA III
Sudden
death
59%
CHF
26%
Other
15%
N=232
NYHA IV
Sudden
death
33%
CHF
56%
Other
11%
N=27 MERIT-HF

126. Athanasuleus CL et al. JACC. 2004;44:1439
Overall five-year survival
Restore TrialRestore Trial
thethe RReconstructiveeconstructive EEndoventricularndoventricular SSurgery returningurgery returning
TTorsionorsion OOriginalriginal RRadiusadius EElliptical shapelliptical shape

127. Stage A
High Risk for
Developing HF
Stage B
Asymptomatic
LV dysfunction
Stage C
Past or current
Symptoms of HF
Stage D
End-stage HF
Stages of HF
Class I
symptoms at activity levels that
would limit normal individuals
Class II
symptoms of HF with
ordinary exertion
Class III
symptoms of HF with less
than ordinary exertion
Class IV
Symptoms of HF at rest
NYHA
Heart Failure (CHF)Heart Failure (CHF)

128. Natural History of DCMNatural History of DCM
DownhillDownhill
IrreversibleIrreversible
High risk for SCDHigh risk for SCD
ProgressiveProgressive

129. PCSD ParacorPCSD Paracor

130. Advanced HeartAdvanced Heart
FailureFailure
Hunt, SA, et al ACC/AHA Guidelines for CHF, ‘01Hunt, SA, et al ACC/AHA Guidelines for CHF, ‘01
Class III-IV:Class III-IV: 40%40%
Mortality/1 yrMortality/1 yr
Class III-IV:Class III-IV: 80%80%
Mortality/2yrsMortality/2yrs
Class IV: 60% Mortality/1 yrClass IV: 60% Mortality/1 yr
ACE-I & Beta Blockade
Reduce Mortality
11,5%
15,6%
12,4%
7,8%
0%
4%
8%
12%
16%
SOLVD-T MERIT-HF
+ CIBIS II
1YearMortality
Placebo Treatment
MortalityMortality
too Hightoo High

131. Therapies for Advanced HFTherapies for Advanced HF
• ANP, BNPANP, BNP
• Endothelin antagonistsEndothelin antagonists
• Vasopeptidase-IVasopeptidase-I
• Cytokine antagonistsCytokine antagonists
• StatinsStatins
• ErythropoeitinErythropoeitin
• IABPIABP
• CRT/ICDCRT/ICD
• Cardiac Support Devices (CSD)Cardiac Support Devices (CSD)
• Cell transplantationCell transplantation
• Total artificial Heart/Total artificial Heart/
permanent LVADpermanent LVAD
Stage DStage D
Refractory HFRefractory HF
requiringrequiring
specializedspecialized
interventionsinterventions
TherapyTherapy
All measuresAll measures
under stages A,B,under stages A,B,
and Cand C
MechanicalMechanical
assist devicesassist devices
HeartHeart
transplantationtransplantation
Continuous (notContinuous (not
intermittent) IVintermittent) IV
inotropic infusionsinotropic infusions
for palliationfor palliation
Hospice careHospice care
Hunt, SA, et al ACC/AHA Guidelines for CHF, ‘01Hunt, SA, et al ACC/AHA Guidelines for CHF, ‘01

132. mRNA Expression for ANP
mRNA Expression for BNP
mRNA Expression of b1-Adrenergic Receptor
mRNA Expression of SERCA-2a
NL HF-Sham HF + CCMNL HF-Sham HF + CCM
mRNA Expression for aMHC
b1-AR
ANP
BNP
aMHC
Serca-2a
Heart FailureHeart Failure
CCM – Mechanisms in HumanCCM – Mechanisms in Human

133. mRNA Expression for ANP
mRNA Expression for BNP
mRNA Expression of b1-Adrenergic Receptor
mRNA Expression of SERCA-2a
NL HF-Sham HF + CCMNL HF-Sham HF + CCM
mRNA Expression for aMHC
b1-AR
ANP
BNP
aMHC
Serca-2a
Unpublishdd dataUnpublishdd data
Heart FailureHeart Failure
CCM – Mechanisms in HumanCCM – Mechanisms in Human

134. De Gasperis Experience
 6 pts: 5 IDC and 1 Ischemic
 NYHA class: III (5 pts) e IV (1 pt)
 LV preop: E.F. 34%, LVEDVi 103 mL
 Associate Procedures : 4 MVR, 1 MCS, 1 CABG
 6 Month Mortality: 0
 LV postop: E.F. 37%, LVEDVi 74 mL
PCSD CorCapPCSD CorCap

135. • MI in anteroseptal portion of LV
• Enlarged LV
• ESV index > 50ml/m2
• EDV index of > 110 ml/m2
• Large area of Akinesis or Dyskinesis
• Asynergy >30% of circumference or 3/10 Echo
anterior segment  STICH Trial
• Acceptable EF of basal portion and lateral wall
• Good RV function
• Candidate for CABG
Inclusion CRITERIAInclusion CRITERIA
“Surgical Ventricular Restoration” (SVR)

136. • MI in anteroseptal portion of LV
• Enlarged LV
• ESV index > 50ml/m2
• EDV index of > 110 ml/m2
• Large area of Akinesis or Dyskinesis
• Asynergy >30% of circumference or 3/10 Echo
anterior segment  STICH Trial
• Acceptable EF of basal portion and lateral wall
• Good RV function
• Candidate for CABG
Inclusion CRITERIAInclusion CRITERIA
“Surgical Ventricular Restoration” (SVR)

137. • As the LV becomes more spherical
this twisting ability of LV reduced
(apical counter-clockwise /basal
clockwise) with reduction both of
LVEF and filling.
• As CHF progresses, the associated
dilation of the LV will often change
both SIZE and SHAPE of LV
Left Ventricular Remodelling
Size, Shape and MV apparatus
• As CHF progresses, the associated
dilation of LV will often pull the MV
apparatus out of proper anatomical
alignment (MR)
• The misalignment reduces the ability
of MV apparatus to assist LV in the
contraction (additional work-load)

138.
Stronger
Directed
Vector
Weaker
Misdirected
Vector
• As the shape of the LV
becomes distorted, this force
vector diminishes
and its direction moves
away from the AoV.
• The result is inefficient
pumping and turbulence in
the LV.
Left Ventricular Remodelling
Aortic Valve

139. • Re-sizing the ventricle around a
Shaper inflated ensures that a
too small or too large ventricle
will not be created.
• The object of SVR should be
the proportional reduction of
both the short and long axis,
because only reducing the long
axis will create a spherical LV,
and lead MR.
• “Surgical Anterior Ventricular Endocardial
Restoration - SAVER”
(TR3
ISVR procedure)
• Shaper defines the new apex.

140. INACTIVE
AREA
Excitabile Gap
Batista Procedure
Arrhythmic Death
NYHA II
Other
24%
CHF
12%
Sudden
death
64%
NYHA III
Sudden
death
59%
CHF
26%
Other
15%
NYHA IV
Sudden
death
33%
CHF
56%
Other
11%