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Spectrum of Acute Coronary Syndrome

Atherothombosis
Acute thrombosis occuring in the presence of pre-existing atherosclerosis producing acute ischemic strokes, acute ischemic syndromes of peripheral arteries and acute coronary syndrome including unstable angina, myocardial infarction (NSTEMI and STEMI) and sudden death.

Milagros Estrada-Yamamoto,MD

Mechanism of Lesion Development

Thrombosis: A Problem of Epidemic Proportions

Over 400,000 deaths annually in Western Europe about 500,000 deaths annually in the United States Cardiovascular Disease - leading cause of death in the Philippines today

Endocrine (DM)

Toxic (nicotine)

Hyperlipidemia

Mechanical (HPN)

Genetic

Combination of Factors

Functional Impairment of Endothelium Increased LDL or other lipid influx Iniation of Inflammation Monocyte Influx Inadequate Wound Healing
Smooth muscle cell proliferation Matrix Deposition Atheroma Formation Thrombus Formation

Terminal Occlusion

Atherosclerosis to Atherothrombosis
Fibrous Cap Lumen Lipid Core

Plaque Vulnerability
Thin fibrous cap (65 um thick). Atheromatous lipid core size greater than 30%. An increased macrophage content. Degree of inflammation (systemic or local). Via hs C- reactive protein

Thrombus
Fibrous Cap

Lipid Core

Stable Plaque

Disrupted Plaque

Stable plaque less than 50% lumen 70% critical because it makes the pt symptomatic Symptoms is not necessary to produce ACS; the basis is as long as there is atherosclerosis Disrupted plaque ACS produce soft thrombus ( can be lyse and reperfuse_

Coronary Artery with Plaque Rupture and Thrombus

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Occurrence of Plaque Complication

Rapid progression Soft plaque

Interaction of Risk Factors, Triggers, and Vulnerable Plaque Triggers

Atherosclerosis Chronic risk factors Acute risk factors: Hemodynamic Vasoconstrictive Prothrombotic

Malleable, plastic, sharp gradients of compliance

Slow progression

Hard plaque

Fixed, inflexible-rigid, fibrotic-calcified

Secondary rapid growth

Fragile plaque

Nonvulnerable plaque

Vulnerable plaque

Disruptible, fibrous cap dissolution, hemorrhage(?)

Disruption, thrombosis

Plaque progression
Unstable Angina Myocardial Infarction Sudden Cardiac Death

Ischemic Triggers
TRIGGER
Exercise Assuming upright posture Cigarette smoking Cold exposure

Possible Trigger for Myocardial Infarction

MEDIATOR
Pulse pressure Heart rate Systolic BP Increased vascular resistance Catecholamine levels

Plaque fissure, Thrombin and platelet activation, and vasospasm

Acute Coronary Syndrome

Unstable Angina Non ST Elevation Myocardial Infarction (NSTEMI)
1,433,000 hospitalizations in USA

Acute Coronary Syndrome

ST Elevation Myocardial Infarction (STEMI)
1,680,000 hospitalizations for ACS in 2001 30% of ACS patients have STEMI 500,000 STEMI events per year in USA

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Unstable Angina and NSTEMI

Imbalance between Oxygen Demand and Supply Non occlusive Thrombus Less severe Ischemia and myocardial damage Unstable Angina Vasospasm

Severe Ischemia and myocardial damage NSTEMI

Hx : Severe localized chest or arm pain at rest or on minimal exertion >20mins, crescendo pattern PE : Pulmonary edema ; New or worsening MR; S3; New or worsening rales ECG : Transient ST segment changes (> 0.05 mv) ; New Bundle branch Block; Sustained Ventricular Tachycardia Cardiac Markers

Pathologic and Clinical Presentation of Acute Coronary Syndromes

Normal

Elevated ( Troponin I, Troponin T, CKMB)

ECG Changes in Unstable Angina/NSTEMI

ST-segment depression (30%) T-wave inversion (20%) Transient ST-segment elevation (5%)
FC

ST Elevation Myocardial Inarction (STEMI)

TH Pathological Diagnosis Coagulation necrosis Prolonged Ischemia Myocytolysis Myocyte Death Clinical Diagnosis Hx - Accelerating Angina and rest pain ( >30 mins ) constricting,crushing,compressing,heaviness,choking Retrosternal radiating to ulnar aspect of left arm Atypical presentation PE Soft S1, S3,S4 ; MR due to papillary muscle dysfunction,pericardial friction rub Hypotension, tachycardia,bradycardia ECG ST segment Elevation, Q waves Cardiac Markers Troponins ( cTnT,cTnI) CK MB mass Myoglobin

LC

Total occlusion

STEMI ECG Findings

STEMI ECG Findings

Occlusion

Occlusion

Anterior Infarction

Inferior infarct

ST segment elevation of at least 1 mm in two or more limb leads

At least 2 mm ST segment elevation in two or more precordial leads

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Revised Definition of Myocardial Infarction (MI)

Criteria for acute,evolving or recent MI Either 1 of the ff :
Typical rise and gradual fall of troponin or rapid rise in CKMB with at least 1 of ff :
Ischemic symptoms Q waves on ECG ST segment elevation or depression PCI

Criteria for Established MI Either 1 of the ff :

Development of new pathologic Q waves on serial ECG Pathologic findings of healed or healing MI (by imaging )

Cardiac Troponins in Acute Myocardial Infarction

Cardiac Troponin T Cardiac Troponin I

Cut-Off Value : 0.04 ng/dl in the cytoplasm Upper Reference Limit : 0.06 ng/dl

Pathological findings

Time course of elevations of serum markers after AMI

Myoglobin
7

Total CK

CK-MB

LDH

Troponin I

Upper limit of normal

6 5 4 3 2 1 0 0 5 10 20 38 40 56 60 72 80 93 100 120 140 160

Likelihood That Signs and Symptoms Represent Acute Coronary Syndrome

Hours from onset of infarction

Myoglobin first to increase and first to go down (1st 1o hrs) not reliable First 4 80 hours troponin I and T more sensitive because CK is elevated in renal problems, usually it is done at the first 6 hours. Dont wait for this result as long as hx and ECG is positive

Feature
History

High Likelihood (any of the ff )

Chest/left arm pain Known hx of CAD

Intermediate Likelihood
Chest/left arm pain Age > 70 Male DM

Low Likelihood
Probable ischemic symptoms with no intermediate characteristics Recent cocaine use Chest pain elicited by palpation T wave flattening or inversion with dominant R waves Normal ECG Normal

Examination

Transient MR, hypotension, diaphoresis, pulmonary edema

Extracardiac vascular disease

Unstable Angina Non ST Elevation MI Acute Ischemia Pathway

ECG

New or presumably Fixed Q waves new ST seg deviation Abnomal ST (> 0.5 mv) segment or T T wave inversion > wave inversion 0.2 mv not new Elevated cTnI, cTnT, CKMB Normal

Cardiac Markers

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Treatment Goals for Unstable Angina and NSTEMI

To stabilize and passivate the acute coronary lesion To treat residual ischemia To employ long term secondary prevention Long term secondary prevention statins it lowers the cholesterol and stabilize the fibrin clot because of its antiinflammatory effect

Acute Ischemia Pathway UA and NSTEMI

General Measures for Unstable Angina And NSTEMI

Admit to monitored bed (CCU) Bed rest Supplemental oxygen Relief of chest pain
Nitrates Beta Blockers Morphine ( 1-5mg/IV )

Antithrombotic therapy
Prevents further thrombosis Allow endogenous fibrinolysis ( spontaneous reperfusion) Long term therapy, to prevent progression to complete occlusion To reduce risk of developing future events

Antithrombotic therapy
Aspirin Clopidogrel Heparin ( UFH and LMWH ) GP IIb/IIIa inhibitors

Aspirin Clopidogrel Heparin Unfractionated and LMWheparin Glycoprotein IIb/IIa inhibitors

The Sequence of Thrombotic Development

1. ADHESION
platelets adhere as a monolayer to the damaged site of the endothelium.

2. ACTIVATION
agonists (ADP, Epinephrine, Thrombin, TxA2) are secreted.

3. AGGREGATION
GP IIb/IIIa receptors bind fibrinogen to form a bridge between other platelets (platelet plug)

Mechanisms of action of antiplatelet therapies

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Antiplatelet Therapy
Aspirin
Block formation of thromboxane A2 in platelets by cyclooxygenase inhibition Initial dose : 162 to 325 mg tab to be chewed Maintenance dose : 75 to 325 mg/day
UFH Loading dose : 75U/kg IV bolus with maintenance infusion of 1250 U/hr titrated to aPTT of 1.5 to 2x control for 2-3 days LMWH dose : 1mg/kg SC BID x 2-8 days

Clopidogrel
Adenosine Diphosphate (ADP) antagonists Inhibit platelet activation Given to patients who are unable to tolerate ASA ( hypersensitivity or GI contraindications,PUD,Gastritis) Initial dose : 300mg loading dose ( 4 tablets) Maintenance dose : 75 mg daily

Mechanisms of inhibitory action of unfractionated heparin (heparin) and low-molecular-weight heparin (LMWH)

Role of GP IIb/IIIa Receptor in Platelet Aggregation

facilitates platelet aggregation by binding w/ fibrinogen Used as an adjunct to primary PCI or thrombolysis Class II a indication of use during primary PCI for STEMI

Anti Ischemic Therapy

Reduce myocardial oxygen demand Prevent Plaque rupture

Abciximab / Eptifibatide/ Tirofiban

Prevention of restenosis 0.25mg/kg IV bolus in 10-60mins before PCI followed by 0.125mcg/kg/min infusion x 12hrs UA not responsive to medical tx 0.25mg/kg IV bolus followed by 18-24 hrs IV infusion 10mg/min

Beta Blockers Nitrates Calcium Antagonists

Coronary and Venodilation

SL NTG 0.4 mg q 5 mins for chest pain IV NTG 1mg/hr to be titrated until relief of chest pain Beta Blockers

O2 Demand

O2 Supply

Mechanism of action of nitrates NO activates soluble guanylyl cyclase, resulting in increased production of cyclic guanosine monophosphate (cGMP). The second messenger cGMP reduces cytoplasmic calcium (Ca2+) by inhibiting inflow and stimulating mitochondrial uptake of calcium, thus mediating relaxation of smooth muscle cells and causing vasodilation
Effects of Beta Blockers on the ischemic heart Beta blockade has a beneficial effect on ischemic myocardium unless (1) the preload rises substantially as in left-sided heart failure or (2) vasospastic angina is present, in which case spasm may be promoted in some patients. Note the proposal that beta blockade diminishes exercise-induced vasoconstriction.

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Beta Blocker Use In ACS

Contraindications ?
HR < 50-60 bpm Systolic BP < 90-100mmHg Severe HF Cardiogenic Shock Asthma or reactive airway disease 2nd or 3rd degree AV block No Yes Avoid use of beta blockers

ACE Inhibitors / A2 Receptor Antagonist Attenuation of Ventricular remodelling Reduction in recurrent MI and ischemia
Decrease in sympathetic activity Improvement in endothelial function Improving hypercoagulable state by decreasing PAI -1
Apical STEMI

Metoprolol / Atenolol
Initial dose Atenolol 25mg BID Metoprolol 50-100mg BID Titration : weekly No Target dose Atenolol 25mg BID Metoprolol 50-100 mg BID Do not abruptly discontinue use ! (Reduce dose gradually in 1-2 weeks)

Oval Spherical

Progressive Ventricular Remodelling To be started within 24 hours of MI Initial dose : Captopril 6.25mg q6-8 max of 50mg TID Enalapril 2.5mg/day max of 20mg BID Lisinopril 2.5mg/day max of 10mg/day

Precautions ?
Heart failure COPD Diabetes mellitus Peripheral vascular disease 1st degree AV block

General Treatment Measures for STEMI

Timely reperfusion of infarcted area ( #1 priority)
Fibrinolysis Percutaneous Catheter Intervention (PCI)

Primary prevention of vascular events

Aspirin Clopidogrel

Control of Cardiac pain

Oxygen Nitrates Beta Blockers Analgesic ( Morphine )

Prevent Ventricular remodelling

Reperfusion ACE inhibitors

Hemodynamic Consequences and Complications of Acute MI

Primary Goal for STEMI : Timely Reperfusion Percutaneous Catheter Intervention (PCI)

Fibrinolytic Agents

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Correlation of TIMI flow grade and mortality Time element if the pt complains of AP; brought in ER in 3 hours, do PCI or fibrinolytic? It will have the same result in first 3 hours. Beyond 3 hours do PCI because fibrinolyitic is not anymore effective

Assessment of Reperfusion Options for STEMI Patients

Assess time and risk
Time since onset of symptoms Risk of STEMI Risk of Fibrinolysis Time required for transport to a skilled PCI lab

Determine if Fibrinolysis or PCI is preferred

( If presentation < 3 hours and no delay to PCI, there is no preference for either strategy )
ACC/AHA Guidelines for the Management of Patients with ST-Elevation Myocardial Infarction, 2004

Fibrinolysis
Preferred if :
Early presentation (< 3 hrs from symptom onset and delay to PCI ) Invasive strategy is not an option
PCI lab occupied or not available Vascular access difficulties Lack of success to a skilled PCI lab

CONTRAINDICATIONS TO FIBRINOLYTIC TREATMENT

Relative Contraindications : Active PUD History of ischemic or embolic stroke in the last 6 months Major trauma or surgery during the previous 2 weeks to 2 months Current use of anticoagulation Chronic HPN w/ diastolic BP > 100 mm Hg Subclavian or internal jugular cannulation

Delay to Invasive strategy

Prolonged transport (Door to Balloon) (Door to Needle) > 1hr Medical contact to balloon > 90 min

Absolute Contraindications : Known bleeding disorder Suspected aortic dissection Prolonged, traumatic CPR Altered consciousness Active internal bleeding Recent head trauma, spinal or intracranial surgery Previous hemorrhagic CVA Major trauma or surgery w/in the previous 2 weeks Persistent HPN > 200 / 120 mm Hg Pregnancy

Percutaneous Catheter Intervention

Preferred if :
Skilled PCI lab available with surgical backup High risk from STEMI
Cardiogenic shock Killips class > 3

Contraindications to Fibrinolysis including increased risk of bleeding and ICH Late presentation
Symptom onset > 3 hr ago

Diagnosis of STEMI is in doubt

Time delay between onset of infarction and restoration of flow in the infarct-related artery
ACC/AHA Guidelines for the Management of Patients with ST-Elevation Myocardial Infarction, 2004

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Transportation of STEMI patients and initial reperfusion treatment

ACC/AHA Guidelines for the Management of Patients with ST-Elevation Myocardial Infarction, 2004

Patient self-transport
ACC/AHA Guidelines for the Management of Patients with ST-Elevation Myocardial Infarction, 2004

Patient with ischemic type discomfort

Rapid triage to urgent care room Aspirin 150-325 mg chewed Goal=10 min Obtain baseline cardiac marker levels Assess initial 12-lead EKG

Recommendations
We could reduce the burden of ACS through :
Nondiagnostic ECG Continue evaluation in ED or short-term observation unit Obtain follow-up serum cardiac markers and ECG Consider 2 D echo

ST elevation

ECG strongly suspicious for ischemia ST depression Tw inversion

Initiate reperfusion strategy Thrombolysis PCI

Admit Initiate antiischemic therapy

Education of patients and relatives about the disease and its attendant risk factors and complications Train healthcare workers and physicians on how to recognize the clinical spectrum of ACS and to be able to administer timely therapeutic strategies following guidelines and protocols

Evidence of ischemia/infarction Yes Routine blood tests to be obtained on admission CBC Lipid profile Electrolyte levels No

Admit Initiate reperfusion strategy if ST elevation develops Discharge

(Goal=6-12 h)

Recommendations
Facility and capability improvement for hospitals and health institutions so that early recognition, observation of symptom progression and prompt delivery of accurate management may be carried out in the Emergency Department, Chest Pain Clinics, Urgency Care Units, Critical Care Units, Cardiac Catheterization and Interventional Units.