Acute Myocardial Infarction

Lenox Hill Heart and Vascular InstituteLenox Hill Heart and Vascular Institute

Acute Myocardial Infarction -Expanding the Therapeutic Paradigm

Howard A. Cohen, MD, FACC, FSCAIDirector, Division of Cardiac Intervention

Co-Director, Cardiac Catheterization LaboratoriesLenox Hill Heart & Vascular Institute

Lenox Hill Heart and Vascular InstituteLenox Hill Heart and Vascular Institute

DISCLOSURE

Consultant, CardiacAssist, IncStock options, CardiacAssist, Inc

Lenox Hill Heart and VascularInstitute of New York


6 RCTs of Primary PCI by Zwolle Group 1994-2001O

ne-Y

ear M

orta

lity

(%)

P=0.001

12

10

8

6

4

2

00 60 120 180 240 300 360

RR=1.08 for each 30 min delay (P=0.04)

Symptom-to-balloon inflation (mins)

DeLuca G et al. Circulation 109:1223, 2004

Time is Outcome: Primary PCI



D2B Time And Mortality2300 Patients

D2B Time And Mortality2300 Patients

Brodie BR, JACC 2006;47:289

High risk = Killip class 3 or 4, age >70, anterior MI



New Devices and Strategies to Manage AMI

REPERFUSION IN AMI AND LV FUNCTION

New Devices and Strategies to Manage AMINew Devices and Strategies to Manage AMI

REPERFUSION IN AMI AND LV FUNCTION

• Reperfusion Rx has resulted in dramatic improvement in survival post MI and has become the standard of care

• Despite improved survival, no significant improvement in LV systolic function has been consistently demonstrated

• This has led to the “open artery hypothesis” to explain improved survival with presumed favorable effects on remodeling, infarct expansion and arrhythmogeneis

• Reperfusion Rx has resulted in dramatic improvement in survival post MI and has become the standard of care

• Despite improved survival, no significant improvement in LV systolic function has been consistently demonstrated

• This has led to the “open artery hypothesis” to explain improved survival with presumed favorable effects on remodeling, infarct expansion and arrhythmogeneis



TREATMENT OF ACUTE MITREATMENT OF ACUTE MI

Goal of Therapy

Restore patencyRestore flow

Restore perfusionRestore function

Improve survival

Goal of Therapy

Restore patencyRestore flow

Restore perfusionRestore function

Improve survival




MICROVASCULAR FLOW IN ACUTE MYOCARDIAL INFARCTIONMICROVASCULAR FLOW IN ACUTE MYOCARDIAL INFARCTIONMICROVASCULAR FLOW IN ACUTE MYOCARDIAL INFARCTION

Microvascular Flow as a Predictor of LV Functional Recovery in Acute Anterior MI

39 patients with acute anterior MI, all with restoration of TIMI III flow

Angiographic successful reflow ≠ successful myocardial perfusion. The MCE defect in the risk area predicts poor functional recovery

Microvascular Flow as a Predictor of LV Functional Recovery in Acute Anterior MI

39 patients with acute anterior MI, all with restoration of TIMI III flow

Angiographic successful reflow ≠ successful myocardial perfusion. The MCE defect in the risk area predicts poor functional recovery

New Devices and Strategies to Manage AMINew Devices and Strategies to Manage AMINew Devices and Strategies to Manage AMI

Ito et al. Circulation 85(5); 1992:1699-1705



Acute MI – The Illusion of ReperfusionAcute MI Acute MI –– The Illusion of ReperfusionThe Illusion of Reperfusion



New Devices and Strategies to Manage AMINew Devices and Strategies to Manage AMINew Devices and Strategies to Manage AMIIs there a better way?• Earliest possible intervention• Improve microvascular flow• Prevent lethal myocardial reperfusion injury• Pharmacologic rx?• LV support?• Resultant improved LV function and decreased

morbidity and mortality

Is there a better way?• Earliest possible intervention• Improve microvascular flow• Prevent lethal myocardial reperfusion injury• Pharmacologic rx?• LV support?• Resultant improved LV function and decreased

morbidity and mortality



Yellon D and Hausenloy D. N Engl J Med 2007;357:1121-1135

Contribution of Lethal Reperfusion Injury to Final MI Size




Major Mediators of Lethal Reperfusion Injury




New Cardioprotective Strategies to ReduceLethal Reperfusion Injury

LV unloadingPre conditioning



Effect of Cyclosporine on Reperfusion Injury in Acute Myocardial Infarction

Christophe Piot, M.D., Ph.D., Pierre Croisille, M.D., Patrick Staat, M.D., Hélène Thibault, M.D., Gilles Rioufol, M.D., Ph.D., Nathan Mewton, M.D., Rachid Elbelghiti, M.D., Thien Tri Cung, M.D., Eric Bonnefoy, M.D., Ph.D., Denis Angoulvant, M.D., Christophe Macia, M.D., Franck Raczka, M.D., Catherine Sportouch, M.D., Gerald Gahide, M.D., Gérard Finet, M.D., Ph.D., Xavier André-Fouët, M.D., Didier Revel,

M.D., Ph.D., Gilbert Kirkorian, M.D., Ph.D., Jean-Pierre Monassier, M.D., Geneviève Derumeaux, M.D., Ph.D., and Michel Ovize, M.D., Ph.D.

N Engl J MedVolume 359(5):473-481

July 31, 2008



Infarct Size by Biomarker Measurement

Piot C et al. N Engl J Med 2008;359:473-481



Infarct Size as a Function of the Area at Risk

Piot C et al. N Engl J Med 2008;359:473-481



LVAD THEORETICAL ADVANTAGES• Superior LV pressure and volume unloading

with enhanced remodeling capability• Decreased wall tension with improved

endocardial blood flow• Beating, non-working heart has low metabolic

requirement• Presumed enhanced ability for cellular repair

and survival

LVAD THEORETICAL ADVANTAGES• Superior LV pressure and volume unloading

with enhanced remodeling capability• Decreased wall tension with improved

endocardial blood flow• Beating, non-working heart has low metabolic

requirement• Presumed enhanced ability for cellular repair

and survival

New Devices and Strategies to Manage AMINew Devices and Strategies to Manage AMINew Devices and Strategies to Manage AMI



LVAD THEORETICAL ADVANTAGES

• Release of cytokines by the heart have been documented in patients post PCI in AMI and implicated in the pathophysiology of CGS

• LVAD support may allow for resolution of these inflammatory and neurohormonal abnormalities with recovery of LV function and hemodynamics – patients who recover are frequently NYHA Class I

LVAD THEORETICAL ADVANTAGES

• Release of cytokines by the heart have been documented in patients post PCI in AMI and implicated in the pathophysiology of CGS

• LVAD support may allow for resolution of these inflammatory and neurohormonal abnormalities with recovery of LV function and hemodynamics – patients who recover are frequently NYHA Class I




LA-FA BYPASS EFFECTIVENESS IN REDUCTION OF EXPERIMENTAL AMILA-FA BYPASS EFFECTIVENESS IN REDUCTION OF EXPERIMENTAL AMI

0

20

40

60

80

100

AI/LV AI/AR TTI MORTALITY

CONTROL LVAD

0

20

40

60

80

100

AI/LV AI/AR TTI MORTALITY

CONTROL LVAD

*

**

*

* p<0.005

Catinella et al. J of Thoracic & Cardiovasc Surgery. 86(6):887-96, 1983

PERCUTANEOUS LEFT VENTRICULAR ASSISTPERCUTANEOUS LEFT VENTRICULAR ASSIST



Methods for Limiting MI Expansion During ReperfusionMethods for Limiting MI Expansion During Reperfusion

0

10

20

30

40

50

60

70

80

C No Aug LA-FA P LA-FA CCP CPB WCP CPB

%AI/AR

Axelrod et al Circulation 76(supplV);28-32,1987



Early LV Support Reduces Infarct Size with Impella®Early LV Support Reduces Infarct Size with Impella®

Minimize Infarct Size = ƒ(Early Support, Extent of Ventricle Unloading)

0%

10%

20%

30%

40%

50%

60%

70%

80%

No Support Full Support (5.0 l)

After Ischemia & Reperfusion

Full Support (5.0 l)

After Reperfusion

Partial Support(2.5 l) After

Reperfusion

Infarct size % of total

area at risk

Meyns, B. et al. J Am Coll Cardiol 2003;41:1087-1095



New Devices and Strategies to Manage AMIPIG MODEL CGS - LVAD vs IABP

EFFECT on MIRCOCIRCULATION

New Devices and Strategies to Manage AMINew Devices and Strategies to Manage AMIPIG MODEL CGS - LVAD vs IABP

EFFECT on MIRCOCIRCULATION

Modified from Hata el al. Artificial Organs. 20(6); 1996:678-680Modified from Hata el al. Artificial Organs. 20(6); 1996:678-680

0

20

40

60

80

100

Epi Q Endo Q Epi Q Endo Q

AMI Shock IABP LHB

*** P < .05* P < .05



TANDEMHEART TO REDUCE INFARCT SIZE

TRIS TRIAL

TANDEMHEART TO REDUCE INFARCT SIZE

TRIS TRIAL• Expanding the Paradigm

Single center safety/feasibility trialFive patients with anterior MILV unloading (TandemHeart) prior to reperfusionInfarct size at 30 days measured by MRIPI – Kirk GarrattDSMB – Chair, David Holmes

• Expanding the ParadigmSingle center safety/feasibility trialFive patients with anterior MILV unloading (TandemHeart) prior to reperfusionInfarct size at 30 days measured by MRIPI – Kirk GarrattDSMB – Chair, David Holmes



• The “up-stream” problems have been been solved to a great extent and now the focus is “down-stream”

• Earlier intervention – clearly beneficial, decrease D to B• Preemptive therapy for protection and restoration of

microvascular flow –Prevent Reperfusion Injury!1. Pharmacology – vasodilators, adenosine, protein kinaseinhibition, cyclosporine, RISK pathway activation2. Myocardial protection- mechanical and metabolic –distal protection, thrombus removal, cooling and enhanced oxygen delivery, pre and post conditioning3. Left ventricular assistance/unloading – pVAD

• Multi-faceted approach required

• The “up-stream” problems have been been solved to a great extent and now the focus is “down-stream”

• Earlier intervention – clearly beneficial, decrease D to B• Preemptive therapy for protection and restoration of

microvascular flow –Prevent Reperfusion Injury!1. Pharmacology – vasodilators, adenosine, protein vasodilators, adenosine, protein kinasekinaseinhibition, cyclosporine, RISK pathway activationinhibition, cyclosporine, RISK pathway activation2. Myocardial protection- mechanical and metabolic –distal protection, thrombus removal, cooling and enhanced distal protection, thrombus removal, cooling and enhanced oxygen delivery, pre and post conditioningoxygen delivery, pre and post conditioning3. Left ventricular assistance/unloading – pVADpVAD

• Multi-faceted approach required

Conclusions: In AMI

THERAPY FOR AMI FUTURE DIRECTIONSTHERAPY FOR AMI FUTURE DIRECTIONS



THANK YOUTHANK YOU

Acute Myocardial Infarction

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