Pathophysiology of

UA/NSTEMI/STEMI

James de Lemos, MD, FACC

UT Southwestern Medical Center
 Disclosures
• Grant Support: Roche Diagnostics and Abbott
Diagnostics
• Endpoint Committee: Ortho Clinical
Diagnostics, Siemen’s Diagnostics
• DSMB: Novo Nordisc, Eli Lilly
 Changing Epidemiology of ACS

Age-adjusted and sex-adjusted

incidence of acute MI in Kaiser
Permanente, Northern
California, USA, 1999-2008

Yeh RW, et al, N Engl Yeh

J Med. al, N Engl J Med. 2010.
RW, et2010.
Pathophysiology of Acute Coronary Syndromes
and Potential Pharmacologic Interventions

4. Downstream from thrombus

myocardial ischemia/necrosis
(Beta-blockers, Nitrates etc)

Fibrin 3. Activation of clotting

Fibrinogen clot cascade - Thrombin
Thrombin (Heparin/LMWH/
IIb/IIIa Fondaparinux/Bivalirudin)
Receptor 2. Platelet adhesion/
activation/aggregation
(ASA, P2Y12 inhibitors,
GP IIb/IIIa inhibitors)
Platelet
1. Plaque rupture,
(Statins)
 Acute Coronary Syndrome

Davies MJ
Heart 83:361, 2000

No ST Elevation ST Elevation
NSTEMI

Myocardial Infarction
Uns Angina NQMI Qw MI
 Vulnerable Plaque

Adapted from Falk E, et al. Circulation. 1995;92:657-671.

 Vulnerable Patient
Generalized Lifestyle
Disorders • Smoking
• Age • Diet
• Obesity • Lack of exercise

Systemic
Conditions
Atherothrombotic • Hypertension
Genetic Traits • Hyperlipidemia
• FH Manifestations
• Diabetes
• Lp (a) (MI, stroke, • Hypercoagulable
• Polygenic vascular death) states
risk

Inflammation
• Elevated CRP
Local Factors
• IL-6
• Blood flow patterns
• Prothrombotic factors Fibrinogen
• Shear stress
• Vessel diameter
MI, myocardial infarction. • Arterial wall structure
Adapted from Yusuf S, et al. Circulation. 2001;104:2746-2753. • % arterial stenosis
Drouet L. Cerebrovasc Dis. 2002;13(suppl 1):1-6.
 Frequency of Multiple “Active” Plaques in
Patients With ACS
80% of Patients With ≥ 2 Plaques

30 N=24

25

20
Patients (%)

15

10

0
0 1 2 3 4 5
Frequency of multiple active plaque ruptures beyond the culprit lesion

Rioufol G, et al. Circulation 2002;106:804-808.

 Type 1: Spontaneous Myocardial Infarction

“Acute coronary atherothrombosis”

… related to plaque rupture, ulceration, fissuring,
erosion, or dissection with resulting intraluminal
thrombus in 1 or more coronary arteries leading to
decreased myocardial blood flow or distal platelet
emboli with ensuing myocyte necrosis. The pt may
have underlying severe CAD but on occasion
non-obstructive or no CAD.
Thygesen et al. Circ 2020.
 Type 2: MI Due to Ischemic Supply/Demand
Imbalance
“Demand MI”
“Secondary MI” (Non-atherothrombotic)

Instances of myocardial ischemia with necrosis where a

condition other than CAD contributes to an imbalance
between myocardial oxygen supply and/or demand, e.g.
anemia, respiratory failure, bradycardia, hypotension,
coronary artery spasm, coronary endothelial dysfunction,
coronary embolism, tachyarrhythmias, and hypertension.

Thygesen et al. EHJ 2012; 33: 2551-2567.

 MI without Plaque Rupture
Variety of Underlying Etiologies
Plaque Rupture/Erosion MVD/Coronary Spasm Dissection Embolism

Rupture Erosion

Cocaine

Takotsubo
Myocarditis Alternate diagnosis
cardiomyopathy

Slide adapted from Harmony Reynolds,

M.D.-NYU
Spontaneous Coronary Artery Dissection
• Prevalence 0.07%-1.1%
• Women: 74-92%
• Mean age 42-52 years
• STEMI, NSTEMI, Sudden
Cardiac Death
• Risk factors
– Woman
– Fibromuscular dysplasia (25-86%)
– Peripartum state (18%)
– Coronary tortuosity
– Connective tissue disorder
– Extreme exertion or emotion

Tweet MS, et al. JACC Cardiovasc Imaging. 2016.