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

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

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

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

No Stenosis

Stenosis

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

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

Unstable

E-KK M-UM

E-IM E-JS

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

00 33 1818 2121 2424 2727 303066 99 1212 1515

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

6.43.9

1.3 1.30 0 0 0 0

101520253035

10 20 30 40 50 60 70 80 90 100

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

millimeters (mm)

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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