1. Acute Coronary Syndrome
Abigail Marie P. Quintos
CV Med Rotation
January 29, 2010

2. Acute Coronary Syndrome
applied to patients in whom there is a suspicion of myocardial ischemia. There are three types of ACS: ST elevation (formerly Q-wave) MI (STEMI), non-ST elevation (formerly non-Q wave) MI (NSTEMI), and unstable angina (UA). The first two are characterized by a typical rise and/or fall in biomarkers of myocyte injury
Anderson, J, Adams, C, Antman, E, et al. ACC/AHA 2007 guidelines for the management of patients with unstable angina/non-ST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2007; 50:e1.

3. Epidemiology STEMI - 30 to 33% NSTEMI - 25% UA - 38 to 42%
Euro Heart Survey ACS
GRACE

5. Unstable Angina
present in patients with ischemic symptoms suggestive of an ACS without elevation in biomarkers with or without ECG changes indicative of ischemia.

6. Acute Myocardial Infarction
a clinical event consequent to the death of cardiac myocytes (myocardial necrosis) that is caused by ischemia (as opposed to other etiologies such as myocarditis or trauma)
Joint task force of the European Society of Cardiology, American College of Cardiology Foundation, the American Heart Association, and the World Health Federation (ESC/ACCF/AHA/WHF) for the Redefinition of Myocardial Infarction. Eur Heart J 2007; 28:2525.

7. NSTEMI
Elevation of cardiac isoenzymes (CKMB or Troponin) and the absence of persistent ST-segment elevation

8. STEMI
Elevated cardiac biomarkers
Presence of ST-segment elevation

9. Pathophysiology
Surface of an atherosclerotic plaque becomes disrupted exposing its contents to the blood, and local or systemic conditions favor thrombogenesis
Mural thrombus forms at the site of plaque disruption and involved coronary artery becomes occluded
Abrupt decrease of coronary blood flow
Harrison’s Principles of Internal Medicine, 17th ed.

10. Clinical Presentation
Precipitating factor:
vigorous physical activity, emotional stress, medical or surgical illness
Chest pain
Weakness, sweating, nausea, vomiting, anxiety, sense of impending doom

11. Chest Pain
not required for the diagnosis of MI, but its presence, may influence decision making about the likelihood of the presence of MI
DEFINITE ANGINA
Substernal discomfort precipitated by exertion, with a typical radiation to the shoulder, jaw or inner aspect of the arm relieved by rest or nitroglycerin in less than 10 minutes

12. Chest Pain in ACS
Three primary presentations that suggest an ACS as opposed to stable or exertional angina:
Rest angina, which is usually more than 20 minutes in duration
New onset angina that markedly limits physical activity
Increasing angina that is more frequent, longer in duration, or occurs with less exertion than previous angina

13. Physical Exam Findings
Anxiety and restlessness
Pallor associated with perspiration and coolness of extremities
25% of Anterior infarcts: Sympathetic (tachycardia, hypertension)
50% of Inferior infarcts: Parasympathetic
(bradycardia, hypotension)

14. Physical Exam Findings
Quiet precordium, AB difficult to palpate
S3 and S4
Decreased intensity of S1
Paradoxical splitting of S2
Transient midsystolic or late systolic apical murmur
Pericardial friction rub (transmural STEMI)
Decreased volume of carotid pulsation

15. AMI: Criteria
Typical rise and/or gradual fall (troponin) or more rapid rise and fall (CK-MB) of biochemical markers of myocardial necrosis with at least one of the following:
      a.  Ischemic symptoms       b.  Development of pathologic Q waves on the ECG       c.  ECG changes indicative of ischemia (ST segment elevation or depression)       d.  Imaging evidence of new loss of viable myocardium or a new regional wall motion abnormality
Pathologic findings (generally at autopsy)

16. Prior/Established MI Pathologic Q waves (≥0.04 sec) on serial ECGs.
patient may or may not remember previous symptoms
Biochemical markers may have normalized, depending upon the length of time that has passed since the MI
Pathologic findings of a healed or healing MI
Evidence from an imaging study of a region of loss of viable myocardium that is thinned and fails to contract, in the absence of a nonischemic cause

17. AMI: Clinical Classification accdg. to assumed proximate cause:
Type 1: consequent to a pathologic process in the wall of the coronary artery (e.g. plaque erosion/rupture, fissuring, or dissection)
Type 2: consequent to inc. O2 demand or dec. supply (e.g. coronary artery spasm, embolus, anemia, arrhythmias, HPN)
Type 3: Sudden unexpected cardiac death before blood samples for biomarkers could be drawn or before appearance in the blood
Type 4a: MI associated with percutaneous coronary intervention
Type 4b: MI associated with stent thrombosis
Type 5: MI associated with coronary artery bypass graft surgery

18. ECG: Cardiac Ischemic Syndromes
ST elevation (Q wave) MI: Q waves usually preceded by hyperacute T waves and ST elevations, and followed by T wave inversions.
Clinically significant ST segment: >1 mm in at least two anatomically contiguous leads, or 2 mm in two contiguous precordial leads.
Non-ST elevation (Non-Q wave) MI: ST depressions or T wave inversions without Q waves.
Isolated T wave inversions correlate with increased risk for MI during initial presentation in the ER
Noninfarction subendocardial ischemia (classic angina): transient ST segment depressions
Noninfarction transmural ischemia (Prinzmetal's variant angina): transient ST segment elevations or paradoxical T wave normalization.

19. ECG: Localization of Ischemia
anatomic location of a transmural infarct is determined by which ECG leads show ST elevation and/or increased T wave positivity:
Anterior wall ischemia - one or more of the precordial leads (V1-V6)
Anteroseptal ischemia - leads V1 to V3
Apical or lateral ischemia - leads aVL and I, and leads V4 to V6
Inferior wall ischemia - leads II, III, and aVF
Right ventricular ischemia - right-sided precordial leads

20. Normal ECG

21. Evolving Anterior MI

22. Right Ventricular MI

23. Biochemical markers

24. Algorithm for initial management of Acute ST elevation myocardial infarction
* Initial laboratory workup include: - Serum cardiac biomarkers (cTnI or cTnT preferred) - CBC with platelet count - PT and INR - aPTT - Electrolytes - Magnesium - BUN - Creatinine - Blood glucose - Serum lipid profile

25. Anti-platelets
ASPIRIN: COX & TXA2 inhibitor, inhibits platelet aggregation
325mg/tab 1 tab chewed
Clopidogrel: inhibits ADP-induces platelet activation
75mg/tab 4 tabs
GP IIb/IIIa inhibitors: inhibits the final common pathway for platelet aggregation
Not indicated in the setting of STEMI unless they are used as an adjunctive to PCI

26. Anticoagulation
Started in NSTEMI patients except those receiving nonselective fibrinolytic agents, or those with a CI to heparin therapy
IV UFH or LMWH (Enoxaparin 1mg/Kg BID) for patients committed to medical therapy or percutaneous revascularization

27. Thrombolytic Therapy
Rapidly lyses the thrombi by catalyzing the formation of serine protease plasmin from zymogen precursor
Eg. Streptokinase, Urokinase, Anistreplase, t-PA
In STEMI: give within 4-6 hours
Absolute contraindications:
Previous hemorrhagic stroke
Other CVA within 1 year
Active internal bleeding
Suspected aortic dissection

28. Antianginal Therapy
NITRATES - vasodilator, dec preload & afterload, inc coronary blood flow
Nitroglycerin – for ischemic chest pain
SL nitroglycerin 0.4mg every 5 mins x 3 doses
IV nitroglycerin drip 10mcg/min, titrated in increments of 10mcg/min every 5 mins until chest pain resolves
BETA BLOCKERS: dec HR BP & Contractility, dec O2 demand
Reduce myocardial ischemia and limits infarct size
Metoprolol 5mg/IV every 5 mins x 3 doses
Avoid in: HF, hypotension with SBP <90, HR <60, 1st d AVB

29. Antianginal Therapy MORPHINE SULFATE
2-4mg/IV every 5 mins until pain disappears or side effects ensue
Adequate analgesia decreases levels of circulating catecholamines and reduces myocardial oxygen consumption
Causes venodilation  decreases preload
Arterial vasodilation
Vagotonic effect  decreases heart rate
Metabolic modulators / pFOX inhibitors (eg. Trimetazidine, Ranolazine)
Inhibit FA oxidation pathway in the myocardium

30. Statins
The Myocardial Ischemia Reduction with Acute Cholesterol Lowering (MIRACL) trial: a new frontier for statins?
Atorvastatin (80 mg/day) initiated 24–96 h after an ACS would, over 4 months, reduce the incidence of the composite endpoint of death, nonfatal infarction, resuscitated cardiac arrest, and recurrent symptomatic myocardial ischemia with new objective symptoms requiring emergency rehospitalization
Indicated in all patients irrespective of baseline levels of LDL

31. ACE inhibitors Reduce peripheral resistance, reduce afterload
Reduce salt and water retention, reduce preload
Reduce angiotensin levels, reduce sympathetic activity
***Reduce the long-term remodeling of the heart and vessels
Eg. Enalapril, Captopril

32. MI Regimen B – beta blockers A – antiplatelets, anticoagulant
T – thrombolytics
M – morphine
A – ACE inhibitor, Atorvastatin
N – nitrates
O – oxygen
L – lactulose

33. The End