vuln shape aha 2005

The Minneapolis HeartInstitute Foundation

The MinneapolisHeart Institute

Perspective:Vulnerable Plaque

…or vessels, patients or ??

Robert S. Schwartz, MDMinneapolis Heart Institute



How to Cure Human Disease

1. Define the Disease2.Associate it reliably3.Find the Disease4. Deliver the ‘Fix’



Arterial Inflammation



Find the DiseaseImaging Technology



3 Autopsy Derived GroupsAcute MI

18 patients/337 segments

Stable Angina 5 Patients/76 segments

Controls (no CAD)9 Patients/111 segments

Coronary Inflammation

Is Diffuse



Inflammatory Cell Count

Macrophages/MonocytesCD-68 Positivity

T-LymphocytesCD-3 Positivity

Coronary Inflammation

Is Diffuse



IRA Segments

AMI

Non-IRA segments

of AMI group

Controls

CD68 positive cells monocytes/macrophages

38.0 + 7.9%

35.3 + 4.7%

1.0+ 2.9%

CD3 positive cells (T-lymphocytes)

17.7 + 3.5%

20.9+ 4.1%

7.6 + 1.6%

Coronary Artery Inflammation Is DiffuseJACC April 2005 Mauriello, Sangiorgi, Fratoni, Palmieri, Bonanno, Anemona Schwartz, Spagnoli



Coronary Inflammation Is Diffuse

05

10152025303540

IRA Non-IRA Control

Macrophages Lymphocytes

JACC April 2005 Mauriello, Sangiorgi, Fratoni, Palmieri, Bonanno, Anemona Schwartz, Spagnoli



Vulnerable Plaque:

Detection



ThermographyWill Thermography will easily detect and localize vulnerable plaque?



Thermography



Porcine Proximal LCX10 days

Histopathology:Chronic, superficial inflammation, mainly mononuclear cells ¾ of the lumen circumflex

Temperature:Circumferential and significantly increasedvessel wall temperature above 1.0°C



Caveat:Thermography and thermal

heterogeneity measures appear highly flow dependent. The methods and devices can be technically challenging. Major differences exist across published studies.



MRIImaging



Self-contained portable MRI

catheter

Catheter Based MRI Imaging



Ex-vivo MR imaging: human coronary arteries

Adaptive intimal thickening

LAD atheroma



VulnerabilityBetter Detection Methods

MSCTA



Coronary Ruptured Plaque (CTA) Aortic Penetrating Ulcer (MRA)



Is Not ‘Soft Plaque”MSCTA visualizes wellQuestions:

Prevalence of isolated Uncalcified Plaque (no associated calcified plaque)

Risk Factors associated

CTA and Uncalcified Plaque



506 unselected patients scanned for chest pain16-Slice MSCTA




30% (124/506 patients) had no calcification


30%70%

No Calcification

Calcification



44% (55/124 patients) had no plaque


30%70%

No Calcification

Calcification



51% (63/124patients) had uncalcified plaque without severe stenosis


51%

49%

No Stenosis

Stenosis



5% (6/124 patients) of Uncalcified Plaque had significant stenosis


5%

95%

SignificantStenosisNo SignficiantStenosis



Risk Factors and all uncalcified plaque83% Smokers (former/current)

98% of patients with 0-3 Risk factors had no plaque or <50% Stenosis

86% of patients with > 4 Risk factors had UCP and/or significant stenosis

No patient with <2 Risk Factors had uncalcified plaque



Uncalcified plaque is prevalent in patients with chest pain

Smoking may have significant impact on UCP formation.

UCP prevalence is highly dependent on aggregate coronary risk.

MSCTA appears useful for detecting both calcified and noncalcified coronary plaque.

MSCTA and Uncalcified Plaque



Observation:Significant technical

developments are needed for MRI. Problems of Spatial and Temporal Resolution, and Acquistion remain a major impediment to clinical coronary imaging in living patients.



Optical Coherence

Tomography



Culprit Lesion

M-OA

M-LC

A-WJ

Unstable

E-KK M-UM

E-IM E-JS

A-MK

RECENT MI

UNSTABLE ANGINA

UNSTABLE ANGINAJust proximal to stented lesion



CaveatIntravascular Imaging can localize thin-cap fibroadenoma and lipid-laden regions of vulnerability.

But what does it mean?



Raman Spectroscopy

Scepanvic O, Galindo LH, Feld MS



Now that we aren’t certain about diagnoses, what about therapy?

Perspective: Imaging Vulnerable Plaque



% % with with EvenEven

tt

00 33 1818 2121 2424 2727 303066 99 1212 1515

2020

1515

1010

55

00

Months of Follow-up

All-Cause Death, Non-Fatal MI, or Urgent Revascularization

Pravastatin 40mgPravastatin 40mg16.7%16.7%

Atorvastatin 80mgAtorvastatin 80mg12.9%12.9%

25% RR25% RRP = 0.0004P = 0.0004



16.7

20.5

33.3

16.7

6.43.9

1.3 1.30 0 0 0 0

05

101520253035

Perc

ent (

%)

10 20 30 40 50 60 70 80 90 100

110

120

130

millimeters (mm) Prox Mid Distal

p = 0.003

Distribution of Acute Coronary OcclusionsLeft Anterior Descending Artery

(Normalized Segment Analysis)



0102030405060708090

1000 10 20 30 40 50 60 70 80 90 100

110

120

130

millimeters (mm)

Perc

ent (

%)

Acute Coronary Occlusions by Distance fromLeft Anterior Descending Artery Ostium



How to Cure Human Disease

1. Define the DiseaseNot Yet

2.Associate it reliablyNot Yet

3.Find the DiseaseNot Yet

4. Deliver the ‘Fix’Not Yet



Perspective:Vulnerable Plaque

…or vessels, patients or ??

Robert S. Schwartz, MDMinneapolis Heart Institute

vuln shape aha 2005

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