Heart Attacks“Mended Hearts” Presentation, January, 2017

Quinn Capers, IV, MDAssociate Professor of Medicine (Cardiovascular Medicine)

Director, Transradial Coronary Interventions

Division of Cardiovascular Medicine

Acute Coronary Syndromes

Definition• Life-threatening episodes of abrupt decrease in coronary blood flow

in the patient with coronary atherosclerotic heart disease

• Continuum (clinical): from unstable angina to ST segment elevation

myocardial infarction (STEMI)

• Clinical continuum correlates with degree of coronary artery

obstruction, from partial to complete.

Stable angina

Unstable angina/

NSTEMI

STEMI

Coronary Atherosclerosis:

Vascular Biology

Acute Coronary SyndromesBiological/Clinical Correlation

• Stable plaque:• Chronic, stable exertional angina pectoris

• Low inflammatory state

• “Chronic coronary syndromes”

• Unstable or “vulnerable” plaque:• Unstable angina, acute MI

• High systemic inflammatory state (CRP, ESR, IL1)

• “Acute coronary syndromes”

1: Excess circulating LDL cholesterol gets sub-

endothelial and becomes oxidized, stimulating an inflammatory

response.

2: Circulating inflammatory cells are attracted to the

subendothelial compartment to participate in the inflammation

3: Once in the subendothelial compartment, the macrophages

ingest the lipid, becoming “foam cells”

4: Accumulation of foam

cells make up the early atherosclerotic

lesion: the “fatty streak”

5: Plaque progression.

Over 20 to 40 years, the plaque continues

To grow, until …

Coronary Artery Plaque/Rupture

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Lessons Learned from Intravascular Imaging

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Coronary Angiogram:

Provides a great silhouette of the lumen

But the action is in the

vascular wall

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Coronary ImagingIntravascular Ultrasound (IVUS)

Unstable/Vulnerable Plaque vs Stable Plaque

Thickness

of fibrous

cap

covering

plaque

Lipids,

WBC’s and

enzymes

within

plaque

Connective

tissue

within

plaque

Risk of

rupture

Associated

clinical

sydromes

Stable

plaque

Thick Small amt Large amt Low Stable

exertional

angina

Unstable/

vulnerable

plaque

Thin Large amt Small amt High Acute

coronary

syndromes,

sudden

death

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Unstable vs Stable Plaque

Acute Coronary SyndromesBiological/Clinical Correlation

Changing the vulnerable plaque to a quiescent, stable plaque is major focus of treatment of CAD patients

Statins (lipid lowering drugs)

BP control

Inhibition of renin angiotensin system

Tobacco avoidance

High Dose Statin Therapy Induces

Regression in Plaque Size and Change in

Plaque Biology

Baseline After 24 months statin tx

Plaque STABILIZATION (Not Regression/Shrinkage) is

the major benefit of aggressive lipid lowering

Lower levels of circulating LDL cholesterol

Less oxidized LDL infiltrating the arterial wall

Fewer macrophages infiltrating the arterial wall

Fewer enzymes to degrade the cap of the plaque

Plaque less likely to rupture

Lower risk of myocardial infarction

Acute Coronary SyndromesPathogenesis of Coronary Thrombosis

Fibrin strands

Platelets

RBC’s

WBC’s

Coronary Thrombosis:Clot begets Clot

Thrombin stimulates

platelet activation

Activated platelets

accelerate thrombin formation

Ruptured plaquepromotes thrombin

formation and recruits platelets

to site

Coronary Thrombosis:

Clot begets Clot

Thrombin stimulates

platelet activation

Activated platelets

accelerate thrombin formation

Ruptured plaquepromotes thrombin

formation and recruits platelets

to site

Antiplatelet drugs

Antithrombin drugs

Antiplatelet drugs

Antithrombin drugs

Antiplatelet drugs

Antithrombin drugs

The Primacy of the Platelet in Acute Coronary Syndromes

Inferior STEMI

100% native RCA

Acute thrombosis

of LAD stent

Keys to breaking the “Vicious Cycle” of Coronary Thrombosis

Antiplatelet drugs Aspirin

Clopidogrel

Prasugrel

IIb/IIIa glycoprotein receptor antagonists

Antithrombin drugs Unfractionated Heparin

Low molecular weight heparins

Bivalirudin

Argatroban

Acute Coronary Syndromes (USA/NSTEMI/STEMI):Treatment Principles

Restore normal coronary blood flow as soon as possible

Address coronary thrombosis, interrupt cycle

Optimize myocardial oxygen demand-supply ratio (Decrease HR, BP, wall tension)

Interrupt sympathetic nervous system/catecholamine stimulation of heart

In STEMI patients and high risk, unstable USA/NSTEMI patients, immediate cardiac cath/reperfusion

Acute Coronary SyndromesTreatment:USA/NSTEMI/STEMI

Statins Reduce inflammation inside culprit plaques and other plaques

throughout the body.

Beta blocker Decrease HR, BP, myocardial oxygen demand

Nitrates Decreases myocardial oxygen demand by decreasing preload, wall

tension

Improves coronary perfusion directly by dilating coronary arteries

Acute Coronary SyndromesTreatment:USA/NSTEMI/STEMI

Clopidogrel/Prasugrel/Ticlopidine/Ticagrelor Inhibits ADP-induced platelet activation

Aspirin Inhibits thromboxane A2-mediated platelet activation

IIb/IIIa platelet receptor antagonists Inhibits final common pathway of platelet aggregation

Reduces composite of death and MI in ACS pts

Unfractionated Heparin or Low molecular weight Heparin Inhibits thrombin

Acute Coronary Syndromes Treatment: USA/NSTEMI/STEMI

When or whether to perform cardiac catheterization with coronary angiography?

In STEMIs---emergently, unless there is a major contraindication

If pain persists despite maximal medical treatment, urgent cardiac cath with revascularization (coronary stent placement or CABG) is indicated

If pain resolves with medical treatment, but patient with high risk markers, cardiac cath and revascularization before hospital discharge (High TIMI Risk Score)

Very low risk patients without recurrent symptoms can be managed conservatively, with cardiac catheterization performed only for recurrent symptoms

Cardiac Catheterization/Coronary Angiography

Acute Coronary Syndromes:

Treatment:STEMI

Lumen

Thrombus

Complex plaque

Acute Coronary Syndromes:Treatment:STEMI

Immediate reperfusion therapy(coronary balloon angioplasty/stent placement or fibrinolytic drug therapy )

Restore normal coronary blood flow ASAP (“Time is muscle”)

Beta blockers, nitrates, antiplatelets, anti-thrombins, and statin drugs are initiated immediately

Acute Coronary SyndromesSTEMI

Fibrinolytic therapy Plasmin: enzyme that digests fibrin strands of a clot, effectively

“lysing” the clot

Plasminogen: Pro-enzyme of plasmin. Needs to be cleaved to plasmin

Plasminogen activators: enzymes that cleave plasminogen to plasmin:

Streptokinase (rarely used in US)

Tissue type plasminogen activator (tPA)

Tnk-tPA (modified tPA with longer half-life)

rPA (modified tPA with longer half-life)

Others (urokinase, APSAC, vampire bat saliva, etc.)

Fibrinolytic therapy: (Plasminogen activators that cleave plasminogen to plasmin)

Plasmin: digests fibrin strands, rendering clot unstable

Antiplatelet agents: prevent further platelet aggregation

Antithrombin agents: prevent production of more fibrin strands

Clot

STEMI: Percutaneous Coronary Intervention (PCI)

Catheter introduced into femoral, Brachial, or radial artery, advanced up to heart

X ray dye injected into coronary arteries to identify blocked artery

Blocked artery opened with tiny balloon and stent

Fibrinolytic drug tx

Improves survival in STEMI pts

Works within 90 min of initiation of tx

Initial success in 65-75% of pts

20-30% of pts reocclude artery

Intracranial bleed in approx 1%

Artery often left with moderate or severe residual stenosis

Available in all hospitals

Percutaneous intervention

Improves survival in STEMI pts

Works within <30 min of initiating cath

Initial success in >95% of pts

<1% of pts reocclude artery

Intracranial bleed risk <0.1%

Artery usually left with 0% residual stenosis

Available in <1/3 of hospitals

Immediate Reperfusion in STEMI: FibrinolyticTherapy vs PCI

STEMI Treatment: Fibrinolytic Therapy vs Percutaneous Coronary Intervention (PCI)

In multiple head-to-head studies, PCI (balloon angioplasty with stent placement) in STEMI pts proved superior to fibrinolytic drug therapy (better survival, better myocardial salvage, lower complication rates)

Most hospitals do not have an interventional cath lab

If pts present to hospitals without cath lab, they have better outcomes if they can be transported to a cath lab and have PCI within 90 minutes

Treatment of STEMI:Coronary Stenting vs Fibrinolytic therapy

Bottom line:

Stenting >>>fibrinolytic therapy>>>nothing

Acute Coronary Syndromes:Treatment:STEMI Whether treating the STEMI pt with fibrinolytic therapy or mechanical

revascularization, patients who receive the treatment early (2-3 hrs from pain onset) have ½ the mortality of people who receive the treatment late (>6 hrs after pain onset)

This is a major problem, with delays at several steps:

Patient delays seeking medical help (denial, poor access, social issues)

Delay in ER staff performing EKG

Delay in EKG being presented to MD for interpretation

Delay in drugs being mixed in pharmacy and administered to pt

Delay in transporting pt from ER to cath lab or from one hospital to another

Delay in cath lab staff coming in from home

Cases from The OSU Ross Heart Hospital

Inferior STEMI

EKG 1615 after ROSC

Sudden Cardiac Death While Exercising

Inferior STEMIArtery Reperfused With Lytic Therapy

Inferior STEMIArtery Reperfused With Lytic Therapy

Inferior STEMIArtery Reperfused With Lytic Therapy

Anterior-Lateral MI with Cardiogenic Shock

Anterior-Lateral MI with Cardiogenic Shock

Anterior-Lateral MI with Cardiogenic Shock

Anterior-Lateral MI with Cardiogenic Shock

Unstable Angina

Unstable Angina

Unstable Angina

Anterior STEMI

Anterior STEMI

Occluded prox-mid LAD

Anterior STEMI

Anterior STEMI

5 Minutes Later . . .

. . .

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Discharge after STEMI: What Rx?

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Acute Coronary SyndromesSTEMI: The Aftermath Therapies to start before hospital discharge:

ACE inhibitors (prevent post-MI cardiac enlargement or “remodeling”, and sudden death)

Statins (decrease lipids and change vulnerable, rupture-prone plaques to stable plaques)

Aldosterone receptor antagonists (improve survival in pts with severe LV dysfunction post-MI)

(These are all in addition to ASA, P2Y12 inhibitor, beta-blocker)

Acute Coronary Syndromes:

Summary• Acute coronary syndromes range from unstable angina without

infarction, to STEMI.

• Stable plaques are filled with connective tissue, are metabolically

inactive, and cause stable exertional angina

• Unstable or “vulnerable” plaques are lipid-filled, tense, metabolically

active, and prone to rupture, causing acute coronary syndromes

• A main focus of treating CAD pts is transforming vulnerable plaques

to stable plaques. Statins are the drugs with the most evidence

supporting this.

Acute Coronary Syndromes:

Summary

• Coronary thrombosis is a hallmark of acute coronary syndromes

• Much of the therapy for ACS is directed at interrupting the vicious cycle of thrombosis (e.g., ASA, clopidogrel, heparin, IIb/IIIa blockers)

• In STEMI, emergent reperfusion can be life-saving, the sooner the better

• In STEMI patients, PCI (coronary stenting) results in greater myocardial salvage and better survival than fibrinolytic therapy, but only if it can be performed expeditiously. If no cath lab is available, do not delay giving fibrinolytic therapy, which is also a life-saving therapy