Acute Coronary Syndrome

DIFFERENTIAL DIAGNOSIS OF CHEST PAIN

Cardiac

Myocardial infarction, angina (atherosclerosis, vasospasm)

Valvular aortic Stenosis

Pericardial Pericarditis

Vascular aortic dissection

Respiratory

Parencymal pneumonia, cancer

Pleural pneumothorax, pneumomediastinum, pleural effusion, pleuritis

Vascular pulmonary embolism

GI esophagitis, esophageal cancer, GERD, peptic ulcer disease, Boerhaave’s, cholecystitis, pancreatitis

Others musculoskeletal (costochondritis), shingles, anxiety

PATHOPHYSIOLOGY

	Pathologic changes	Clinical presentation
Pre clinical	Atherosclerosis	Asymptomatic
Angina	Luminal narrowing	Central chest discomfort; worsened by exertion, emotion, and eating; relieved by rest and nitroglycerine
Unstable angina	Plaque rupture or thrombus	Worsening pattern or rest pain
NSTEMI	Partial occlusion	Non ST elevation MI
STEMI	Complete occlusion	ST elevation MI

Universal Definition of Myocardial Infarction (MI)

TYPE 1 spontaneous MI due to a primary coronary event (atherosclerotic plaque rupture or erosion with acute thromboembolism)

TYPE 2 MI due to supply demand mismatch

TYPE 3 MI associated with sudden unexpected cardiac death

TYPE 4 MI associated with PCI (4A) or stent thrombosis (4B)

TYPE 5 MI associated with CABG

Risk Factors

Major diabetes, hypertension, dyslipidemia, smoking, family history of premature CAD, advanced age, male gender

Associated obesity, metabolic syndrome, sedentary lifestyle, high fat diet

Emerging lipoprotein abnormalities, inflammation (increased in level CRP), chronic infections, renal failure.

Post MI Complications arrhythmia (VT/VF, bra dycardia), sudden death, papillary muscle rupture/dysfunction, myocardial rupture (ventricular wall, interventricular septum), ventricular aneurysm, valvular disease (especially acute mitral regurgitation), heart failure/car diogenic shock, pericarditis (Dressler’s syndrome)

CLINICAL FEATURES

Chest Pain Equivalents dyspnea, syncope, fatigue, particularly in patients with diabetic neuropathy who may not experience chest pain

New York Heart Association (NYHA) Classification

I = no symptoms with ordinary physical activity

II = mild symptoms with normal activity (walking >2 blocks or 1 flight of stairs)

III = symptoms with minimal exertion

IV = symptoms at rest

Canadian cardiovascular society (CCS) Classification

I = angina with strenuous activity

II = slight limitation, angina with meals/cold/stress

III = marked limitation, angina with walking < 1 to 2 blocks or 1 flight of stairs

IV = unstable angina

    IVA= unstable angina resolves with medical treatment

    IVB = unstable angina on oral treatment, symptoms improved          but angina with minimal provocation

   IVC = unstable angina persists, not manageable on oral treatment     or hemodynamically unstable

Killip class classification

I = no evidence of heart failure

II = mild to moderate heart failure (S3, lung rales less than half way up, or jugular venous distension)

III = overt pulmonary edema

IV = cardiogenic shock

Rational clinical examination series: Is this patient having a myocardial infarction?
	LR+
History
Radiation to right shoulder	2.9
Radiation to left arm	2.3
Radiation to both arms	7.1
Nausea or vomiting	1.9
Diaphoresis	2.0
Pleuritic chest pain	0.2
Sharp or stabbing chest pain	0.3
Positional chest pain	0.3
Chest pain reproducible by palpation	0.2  0.4
Physical
Hypotension	3.1
S3	3.2
Pulmonary crackles	2.1
ECG
New ST elevation >1 mm	5.7 53.9
New Q wave	5.3 24.8
Any ST elevation	11.2
New conduction defect	6.3
New ST depression	3.0 5.2
Any Q wave	3.9
Any ST depression	3.2
T wave peaking or inversion >1 mm	3.1
New T wave inversion	2.4 2.8
Any conduction defect	2.7
APPROACH ‘‘radiation of chest pain, diaphoresis, hypotension, and S3 suggest acute MI. Chest pain that is pleuritic, sharp or stabbing, positional or reproduced by palpation decreases likelihood of acute MI. On ECG, any ST ", new Q waves, or new   conduction D make acute MI very likely. Normal ECG is very powerful to rule out MI’’

INVESTIGATIONS

Basic

Labs CBCD, electrolytes, urea, Cr, glucose, troponin/ CK 3 q8h, AST, ALT, ALP, bilirubin, INR/PTT, Mg, Ca, PO4, albumin, lipase, fasting lipid profile, HbA1C

Radiography CXR, echocardiogram (first 72 h), MIBI/thallium (>5 days later)

ECG q8h 3 or with chest pain

Stress Test ECG, echocardiogram, MIBI once stable (>48 h post MI)

Coronary Catherization

DIAGNOSTIC AND PROGNOSTIC ISSUES

Risk Stratification for stable Coronary Disease

ECG exercise test

Absolute contraindications recent myocardial infarction (>4 days), unstable angina, severe symptomatic LV dysfunction, life threatening arrhythmia, acute pericarditis, aortic dissection, PE, severe symptomatic aortic Stenosis

Goal keep on treadmill until subject reaches 85 90% of age predicted heart rate (220 age).

Ischemia Criteria >1 mm horizontal or down sloping ST decreased level over multiple leads, or ST increased level —> myocardial ischemia (sens 68%, spc 77%) —> proceed to angiogram

Inclusive premature termination due to chest pain/poor exercise tolerance —> proceed to pharmacological stress test.

Duk Treadmill Score (exercise time in minutes) 5x(maximum ST decreased level in mm)  4x(tread mill angina index [0=none, 1=non limiting, 2=exercise limiting]). Low risk > 5 (4 year survival 98 99%), , moderate risk 10 to +4, high risk < 11 (4 year survival 71 79%)

DIipyrid/Adenosive MIB dipyridamole (Per santine) causes vasodilation. In CAD, the coronary artery is already maximally dilated to compensate, so addition of dipyridamole will not change perfusion to diseased vessel(s) further. This result in a relative perfusion mismatch compared to areas with normal dilatory reaction. Contraindicated in asthma/COPD. Antidote is aminophylline or caffeine

Dobutamine Echocardiography assesses wall motion abnormalities. Compared to MIBI, echo cardiogram is more specific and less sensitive. Contraindicated in severe hypertension and arrhythmias

Diagnosis of stable CAD start with history, physical, rest ECG, and CXR. If low probability, do not investigate further. If high probability, proceed with management. If intermediate probability —> stress test —> cardiac CT, MIBI or stress echo —> angiography

Differential, Diagnosis of Troponin Elevation Cardiac myocardial infarction, myocarditis, congestive heart failure, pericarditis, vasospasm, tachycardia with hemodynamic compromise, cocaine ingestion

Pulmonary embolism

Hepatic liver failure

Renal chronic kidney disease

Neurologic stroke, intracranial hemorrhage

Systemic sepsis, prolonged strenuous exercise

Serum Markers

Troponin I/T rises within 4 6 h, peaks at 18 24 h, remains elevated 7 10 days (sens 40% at presentation, 40 70% after 6 9 h of symptoms)

CK/CKMB rises within 4 6 h, peaks at 18 24 h, remains elevated 3 4 days (sens 35 50% at presentation, 90% after 3 h in ER)

Myoglobin rises within 1 2 h, peaks in few hours

TIMI Score patients with unstable Angina/NSTEMI

Scoring (out of 7) age > 65, > 3 CAD risk factors, known CAD (stenosis > 50%), ASA use within 7 days, > 2 angina episodes within 24 h, " cardiac marker, ST deviation >0.5 mm

Risk Groups low = 0 2, intermediate = 3 4, high = 5 7. Consider GPIIb/IIIa and early angiography with revascularization in intermediate or high risk groups

Risk of death, MI or Revascularization in 14 days 0/1 = 5%, 2 = 8%, 3 = 13%, 4 = 20%, 5 = 26%, 6/7 = 41%

TIMI Score for patients with STEMI

Scoring (out of 14) age (3 points= > 75, 2 points=65 74), any of diabetes, hypertension, or angina (1 point), systolic BP < 100 mmHg (3 points), HR > 100 (2 points), Killip II IV (2 points), weight < 67 kg (1 point), anterior ST elevation or LBBB (1 point), time to reperfusion >4 h (1 point)

Risk of death in 30 dyas 0=0.8%, 1=1.6%, 2=2.2%, 3=4.4%, 4=7.3%, 5=12.4%, 6=16.1%, 7=23.4%, 8=26.8%, >8=35.9%

In Hospital Outcomes
	NSTEMI	STEMI
Death	4%	6%
Reinfarction	0.9%	1.1%
Cardiogenic shock	2.8%	6.4%
Stroke	0.7%	0.8%
Major bleeding	10%	12%

 ACUTE MANAGEMENT

ABC O2 to keep sat >95%, IVs, inotropes, consider balloon pump if hemodynamic instability

Pain Control nitroglycerin (nitro drip 25 mg in 250 mL D5W, start at 5 mg/min IV, then increased by 5 by 5 10 mg/ min every 3 5 min to 20 mg/min, then increased by 10 mg/ min every 3 5 min up to 200 mg/min, or until relief of pain, stop titration if SBP is < 100 mmHg. Nitro patch 0.4 mg/h daily. Nitro spray 0.4 mg SL q5min x3. Beware if suspect right ventricular infarction or if patients on sildenafil). Morphine 2 4 mg IV every 5 15 min PRN.

Clot Control

Antiplatelet ASA 162 325 mg PO chew x 1 dose, then 75 162 mg PO daily (for medically treated unstable angina/NSTEMI), or 162 325 mg PO daily (post PCI minimum x 1 month for bare metal stent, x 3 months for sirolimus eluting stent, or x 6 months for paclitaxeleluting stent), then 75 162 mg PO daily indefinitely. If NSTEMI or STEMI, clopidogrel 300 600 mg x1 dose then 75 mg PO daily. Combination ASA plus clopidogrel for minimum of 1 month (ideally 1 year) post PCI with bare metal stent, or minimum 12 months (possibly indefinitely) for drug eluting stents. If post PCI, pain unresponsive to nitroglycerin or intermediate/high risk NSTEMI, consider GPIIb/IIIa inhibitor (tirofiban 0.4 mg/kg/min 30 min IV, then continue 0.1 mg/kg/min x 18 24 h after angioplasty/atherectomy. Eptifibatide 180 mg/kg IV bolus, then 2 mg/kg/min x 72 96 h)

Anticoagulation options include LMWH (enoxaparin 30 mg IV bolus, then 1 mg/kg SC BID for STEMI [no IV bolus for NSTEMI caution if renal failure or age > 5) or unfractionated heparin (unfractionated heparin 70 U/kg [up to 4000U] IV bolus, then 18 U/kg/hr [up to 1000U/h] and adjust to 1.5 2.5 x normal PTT for 72 h). Factor Xa inhibitors (Fondaparinux 2.5 mg SC daily until discharge or 8 days, caution if renal failure). Direct thrombin inhibitors (Bivalirudin 0.1 mg/kg IV bolus then 0.25 mg/kg/hr initially, followed by second 0.5 mg/kg bolus before PCI and 1.75 mg/ kg/hr during PCI, then continue infusion for up to 4 h post PCI, if needed)

Rate Control IV metoprolol is mostly contra indicated. Start with metoprolol 25 mg PO BID and titrate slowly. Alternatively, atenolol 25 mg PO daily and titrate to 100 mg PO daily. The goal heart rate is 50 55 with normal activity. If b blocker contraindicated, consider non dihydropyridine calcium channel blockers diltiazem 30 120 mg PO QID or verapamil 80 120 mg PO TID (contraindicated if LV dysfunction)

Lipid Control simvastatin 40 mg PO daily or atorvastatin 80 mg PO daily

Blood Pressure Support for patients with cardiogenic shock, consider IV fluids, inotropes (dobutamine/dopamine), balloon pump, and early revascularization

Cautions in treatment of acute myocardial infarction avoid negative inotropic agents such as b blockers and non dihydropyridine calcium channel blockers if clinical heart failure. Avoid administration of nitroglycerin, morphine, and diuretics to patients with right ventricular infarction as these medications can cause venodilation and decrease preload, leading to hypotension.

LONG TERM MANAGEMENT OF CORONARY ARTERY DISEASE

Antianginal nitroglycerin (nitro patch 0.4 0.8 mg/h daily; nitro spray 0.4 mg SL q5min 3; isosorbide mononitrate 30 mg PO daily, maximum 240 mg), b blocker (metoprolol 25 100 mg PO BID, atenolol 50 100 mg PO daily, bisoprolol 5 10 mg PO daily), calcium channel blocker (amlodipine 5 10 mg PO daily)

ACE Inhibitor ramipril 2.5 10 mg PO daily

Ant platelet ECASA 81 mg PO daily and/or clo pidogrel 75 mg PO daily

Anticoagulation controversial especially in combination with ASA and/or clopidogrel. May be considered for patients post STEMI or NSTEMI with one of the following criteria: (1) atrial fibrillation, (2) left ventricular thrombus, (3) significant left ventricu lar dysfunction with extensive regional wall motion abnormalities. Start warfarin 5 mg daily within 72 hours and continue heparin/LMWH until INR is between 2 and 3 (unless planning angioplasty)

Risk Reduction

ASA/ACE Inhibitor

Blood Pressure Control

Cholesterol Control

Diabetic Control

Exercise (30 min of moderate intensity exercise 3 4x /week)

Fat Redyction

Get going to quit smoking!

TREATMENT ISSUES

Right Ventricular Infarction evidence of inferior MI should automatically trigger one to check right sided leads (V4R) to assess for the possibility of RV infarction, which occurs in about 50% of patients with inferior MI.

Posterior Infarction ST depression in V1 V2 in a regular ECG should automatically trigger one to request for posterior (V7 V9) leads to check for posterior MI. Posterior infarct may be associated with inferior infarcts (90%) and lateral infarcts (10%) as the PDA may be supplied by the right or left circum flex coronary artery

Post MI Risk Stratification

Extent of Infarct/Residual Function assessment is based on clinical factors (raised HR, decreased BP, Killip class, diabetes, renal failure, raised WBC), ECG, biomarkers (CK, troponin), imaging (echocardiogram, MIBI), and angiography. Early measurement of LV function, although of prognostic importance, is misleading as myocardium function may improve in first 2 weeks. Medical management

Extent of Myocardium at risk assessment is based on exercise stress test, stress echocardiogram, stress sestamibi (ischemic tissue), thallium scan (viable tissue), PET scan, angiography. Angioplasty or CABG should be considered.

Risk of Arrhythmia high risk of VF/VT within the first 48 h, therefore monitor with telemetry. If it occurs after 48 h, consider antiarrhythmics and early ICD

Balloon Pump a long balloon in the descending aorta that deflates during systole and inflates during diastole to augment coronary perfusion and cardiac output as well as decrease after load. Indicated if cardiogenic shock with hemodynamic instability. May be used in conjunction with inotropes. Contra indicated in aortic regurgitation, AAA, aortic dissection, uncontrolled sepsis bleeding disorder, and severe PVD

Fibrinolytics use (TPA, SK, RPA, TNK)

Indications > 30 min of chest pain, patient presents within 12 h (ideal door to needle time < 30 min), ECG criteria (>1 mm ST " in > 2 contiguous leads, or new LBBB with suggestive history, age < 75)

Absolute Contraindications any intracranial hemorrhage, ischemic stroke within 3 months, cerebral vascular malformation or brain tumor, closed head or facial trauma within 3 months, suspected aortic dissection, bleeding diathesis, or active bleeding

Relative Contraindications severe hypertension (>180/110 mmHg, may be an absolute contraindication for patients at low risk), ischemic stroke > 3 months, other intracranial diseases not already specified above, dementia, internal bleeding within 2 4 weeks, active peptic ulcer, major surgery within 3 weeks, non compressible vascular punctures, cur rent warfarin therapy, pregnancy, traumatic CPR > 10 min, prior exposure to streptokinase or anistreplase (if planning to use these fibrinolytics)

Risk of Bleeding average risk of severe bleed is 1.8%. Increased risk with women, BP > 165/ 95 mmHg, age > 65, weight < 70 kg [<154lbs], and electrolysis with TPA (+0.5% absolute risk/factor)

Persistent ST Elevation look for resolution of symptoms and ST elevation to decrease by >50% within 90 min of fibrinolytic therapy. Persistent ST elevation may suggest failed fibrinolytic therapy, and require urgent rescue catheterization. Other causes of ST elevation include pericarditis, ventricular aneurysm, hyperkalemia, LBBB, and early repolarization abnormality.

Percutaneous Coronary Intervention (PCI, PTCA)

Indication for acute STEMI patient presents within 12 h of chest pain (ideal time from initial medical contact to treatment or ‘‘door to balloon time ’ < 90 min), ECG criteria (>1 mm ST increased in > 2 contiguous leads, new or presumed new left bundle branch block), or in patients in cardiogenic shock within 18 h of infarct

Indications for Chronic Stable CAD single/ double vessel disease refractory to medical therapy.

Adverse events access site (bleeding, hematomas, arteriovenous fistulae, pseudoaneurysms), contrast nephropathy, arrhythmia (VT, VF), stroke, dissection, myocardial infarction.

Bare metal Stents vs. Drug-Eluting Stents in stent restenosis is due to fibrosis of coronary vasculature and usually happens 3 months post procedure. Drug eluting stents (sirolimus or pacli taxel) are designed to inhibit cell proliferation and decrease the risk of in stent restenosis. There has been some controversy regarding higher observed mortality rate in patients with drug eluting stents. The most recent outcomes research analysis suggests that drug eluting stents are associated with decreased rate of repeat revascularization (19% vs. 23%, HR 0.82) at 2 years and no significant difference in mortal ity (8.4% vs. 8.4%)

Benefits primary PCI is generally preferred given the superior outcomes compared to fibrinolysis, particularly if (1) fibrinolysis contraindicated, (2) previous history of CABG, or (3) cardiogenic shock. However, patients who were able to seek medical attention within 1 h of chest pain onset, allergic to contrast dye, or do not have access to PCI in a timely fashion should consider fibrinolytics

Coronary Artery Bypass Graft Surgery

Coronary Anatomy

Right Coronary Anatomy (RCA) gives rise to right marginal (RMA), right posterior descending (RPDA), and right posterolateral branches (RPL 1, 2, 3)

Left Main (LM) gives rise to left anterior descending (LAD) ͢   ! diagonal (D1, 2 3) and septals; ramus intermediate (Ram Int); and left circum flex (LCX) ͢  obtuse marginal (OM 1, 2, 3)

Dominant Artery defined as the artery that sup plies PDA and at least one posterolateral (PL) artery

Indications CABG provides mortality benefit for specific subgroups, including patients with

1) left main disease >50% occlusion,

2) 2 vessel disease with significant involvement of proximal left anterior descending, and

3) diffuse triple vessel disease. Diabetic patients and those with reduced left ventricular function derive more benefit from bypass surgery

Morbidity Benefit 95% have improvement of symptoms immediately after surgery, 75% symptom free at 5 years. Recurrent disease more common in vein grafts than artery grafts

Grafts saphenous veins from calf or thigh (SVG), internal mammary arteries (LIMA/RIMA), radial arteries (RA), and gastroepiploic artery from sto mach (GA). A total of 90% of arterial graft and 50% of vein graft remain patent by 10 years

Complications

Cardiac MI 2 4%, arrhythmia (AF 40%, sustained VT/VF 2 3%), AV block requiring pacemaker 0.8 4%, pericarditis/tamponade, aortic dissection

Neurological stroke, postoperative delirium, cognitive impairment, depression, phrenic nerve damage, intercostal nerve damage

Others renal failure, bleeding, infection, pleural effusions

Medications hold clopidogrel 5 7 days prior to CABG. Continue ASA before and after surgery.