1. CORONARY ARTERY DISEASE/MI
By Henri Godbold MD
Med Peds
Noon Conference 9/21/2006

2. ETIOLOGY Manifestation of atheroma with preserved caliber of lumen
Rupture of the plaque’s fibrous cap causing a thrombosis
The clot overwhelms the endogenous fibrinolytic mechanism may propagate and lead to occlusion

3. CLINICAL MANEFESTATIONS
Transient ischemic cardiac events if prolonged can lead to necrosis and scarring with or without MI
Patients can present with cardiomegaly and heart failure secondary to ischemia of damage left ventricle

4. ANGINA Chest pain caused by mismatch of myocardial O2 supply & demand
Classified as:
Stable (usually from concentric plaque)
Usually 2º atherosclerotic obstruction
Unstable (usually from an ulcerated, ruptured plaque)-nidus for platelet aggregation
New onset or increased frequency
Only about 20% of pts. with ischemic ST changes have classic angina

5. ANGINA TREATMENT
Modify risk factors & correct aggravating factors (anemia, HTN, drug abuse, non-compliance)
Emphasize meds. known to prolong survival post-MI
ASA also should be standard therapy
CCRB and nitrates may be useful for symptoms
Careful with combining meds. with similar effects (ie. Beta blockers, and verapamil)

6. ASSOCIATED SYMPTOMS Dyspnea Diaphoresis Dizziness Syncope Palpations
Deep breathing pain
Nausea and vomiting
Edema
Orthropnea
Paroxysmal nocturnal dyspnea
Positional pain

7. CARDIAC RISK FACTORS Absolute FH smoking DM HTN Hyperlipidemia
(LDL> 130, HDL<35)
AGE (men>45,Female>55)
Relative
Obesity
sedentary life
stress
postmenopausal state
OTHER
Hx CVA and PVD disease

8. ROLE OF INFLAMATION AS A RISK FACTOR
Vascular injury
Lipid peroxidation: along with the effects of HTN, DM, and smoking amplify the harmful effects of oxidized LDL cholesterol
Chronic inflammation promoting athersclerotic plaque which rupture and thrombose in vessels

9. CIRCULATING MEDIATOR Inflammatory process: Acute phase reactants
Cell adhesion molecules
Inflammatory Markers-
C-reactive protein (CRP)
IL-6
serum amylase A
TNF alpha
selectins
macrophage inhibitor cytokines 1
CD40 ligands

10. Characteristic of CRP High sensitivity Assay well standardized
Widely available
Strong predictor of future myocardial infarctions and stroke
High plasma concentration are associated with a 1.5-to-7 fold increase in the relative risk of symptomatic atherosclerosis

11. Role of homocysteine in risk stratification
Statistically significant but modest
increase in risk of CAD events
Folic acid can reduce serum elevation
Neither prospective or randomized trails
show reduction in elevation reduces CHD
risk
Routine measurement are not warranted

12. MANAGEMENT APPROACH
Goals are reduce coronary morbidity and mortality via:
Primary prevention: reducing risk of first
event
Secondary prevention: reducing risk of
event in person with established
disease

13. Correct reversible risk factors: smoking, hypertension, uncontrolled DM, obesity, stress, life style modification
Risk Stratification (Table 27.4)

14. CAD Risk Association with Lipoprotein Cholesterol Abnormalities
Levels (mg/dl)
Estimated
CHD Risk
LDL
<130
low
moderate
>160
high
HDL
>65(chol/HDL ratio >4.5)
<35(chol/HDL ratio <4.5)
Mod-high
VLDL
50-100(or fasting TG )
>100(or fasting TG >500)
? high

15. DIAGNOSIS
First step: estimate pretest probability base on know CV risk factor(age, gender) and symptoms) Is as follows:
Low(<10%):
- Asymtomatic men and women of all
ages
- Women younger than 50 yrs or order
with typical angina

16. Intermediate (10%-90%): High (>90%):
Men of all ages with atypical angina
Women 50yrs or older with atypical angina
Women 30-59yrs with typical angina
High (>90%):
Men 40yrs or older with typical angina
Women 60yrs or older with typical angina

17. TESTING MODALITIES Cardiac Stress Testing:
Preferred approach to assessing CAD in patients with suspected or known disease
Goal to induce myocardial ischemia by increasing myocardial oxygen demand
Indicated for the diagnosis of myocardial ischemia
Indicated for ECG abnormalities WPW, >1mm resting ST depression, LBBB
After cardiac catherization to identify if ischemia is present in the distribution of the coronary lesion identified

18. Exercise Stress Test Preferred to pharmacologic stress
Provides data on exercise capacity and hemodynamic response to exercise
Patients with normal baseline ECG, ischemia can be detected using ECG monitoring
Patient with abnormal baseline ECG, who undergo pharmacologic or exercise stress testing, either echocardiographic or radionuclide imaging is needed to detect ischemia

19. Stress Echo
Detects provoked regional ventricular wall motion abnormality
Uses myocardial perfusion imaging:
Sestambi(Cardiolite) radionuclide tracer, decrease uptake represent the area of ischemia measure by scintigraphy
Vasodilator agents: Adenosine, Persantine and dobutamine

20. Postitron Emission Tomography(PET)
More specific and sensitive than conventional nuclear imaging
Can combine high resolution CT imaging of anatomy and function for noninvasive assessment of coronary disease

21. Coronary Angiography Invasive Pretest probability of disease is high
Stress test is positive
Symptomatic presentation despite a negative stress test
Diagnosis and therapy can be preformed simultaneosly (i.e. percutaneous revascularization)

22. Indication Revascularization in Patient with Chronic Stable Angina
CABG is recommended for
Left main coronary artery stenosis
3-vessel CAD(greatest survival benefit with EF <50%)
2-vessel CAD and proximal LAD stenosis with LV EF <50% or ischemia on noninvasive testing
1-2 vessel CAD w/o prox LAD stenosis who survived sudden cardiac death or sustain VT

23. Percutaneous Coronary Intervention (PCI) is recommended for
Nondiabetics w/ 2-vessel CAD
Proximal LAD stenosis
Normal LV function w/ anatomy amenable to PCI

24. Either CABG or PCI recommended
1 or 2 vessel CAD w/o prox LAD stenosis and high risk criteria on noninvasive testing
Prior CABG or PCI w/ recurrent stenosis and a large area of ischemia or high risk criteria on noninvasive testing
Symptoms refractory to medical therapy with an acceptable risk of revascularization

25. TREATMENT
Vigorous lifestyle modification- low fat and cholesterol diet; regular exercise; and smoking cessation
Aspirin- antiplatelet
Statin- lipid-lowering
Beta blocker and CCB- reducing myocardial oxygen consumption
ACE inhibitor-especially patients w/ DM and /or left ventricle systolic dysfunction

26. Nitrates: reduce angina by peripheral venodilation and coronary artery dilation
To avoid tolerance need atleast 8hrs daily free period
Do not use in patients receiving phosphodiesterase type 5 inhibitors( sildenafil, vardenafil, tadalafil) lead to life threatening hypotension

27. Hyperlipidemia Drugs HMG-CoA reductase inhibitor (Statins) First line
Inhibits intracellular cholesterol and increase clearence LDL
Starting dose 10-20mg/d w/ max dose 80mg/d
Adverse effects hepatocellular dysfunction and myositis
Monitor transaminases intially then f/u measurements 6 month and 1 year

28. Bile Acid Sequestrants
Interrupt enterohepatic circulation in the gut
Highly effective used in combination in those high risk patients
Side effects constipation, bloating, heartburn and nausea

29. Ezetimibe
Block absorption from the gut
Inhibits cholesterol transport by interfering with specific transporters proteins and dose not interfering w/ other drugs and fat-soluble vitamins
Lowers LDL by 15 to 20%; If use with statin, provides additional 15% reduction

30. Niacin( B-complex vitamin)
Inhibits mobilization of free FA from fat cells to the liver
Raises HDL 15% to 35%
Lowers triglycerides 20% to 50% and LDLs 5% to 25%
Side affects flushing, pruritis, PUD, hyperglycemia, rashes

31. Fibrates(Gemfibrozil and Fenofibrate)
Not first-line
Decreases VLDL synthesis enhancing clearance
Raises HDL cholesterol
Well tolerated except in combo w/ statins possible rhabdomyolysis

32. Nonprescriptions dietary Supplements
Omega-3 Fish Oils
Decreases VLDL, and platelet inhibition
Antioxidant vitamins
Capable of increasing LDL resistance to oxidative changes and reduce the risk of arterial wall injury
Garlic, Fiber, and Red yeast extract

33. Treatment Thresholds Recommendation of NCEP Panel
High risk or CAD plus multiple risk factor
LDL cholesterol threshold 100mg/dl, treatment goal <70mg/d
Moderately high risk(no CAD, multiple risk factor and 10 yr CAD risk 10%-20%)
LDL cholesterol threshold 130mg/dl, treatment goal <100mg/dl

34. Moderate risk with 2 or more CAD risk
Factors (10yr risk probability is <10%)
LDL cholesterol cut off 160mg/dl
Fewer than 2 CAD risk factors
LDL cholesterol >190mg/dl require drug rx
Optional rx for levels between mg/dl

35. Isolated low HDL cholesterol
Treatment with statin seems to lower CAD morbidity
Even though the strong inverse relationship between HDL levels and CHD risk, there is no data showing that raising HDL alone significantly reduces CAD mortality

36. Primary Prevention Secondary Prevention
NECP target LDL Cholesterol <130mg/dl, ATPIII optimal level <100mg/dl and target of less than 100mg/dl for person with moderate high CAD risk
Secondary Prevention
LDL cholesterol < 100mg/dl with an optimal goal of <70mg/dl for very high risk patients

37. ACUTE MYOCARDIAL INFARCTION(AMI)
Overview
15% are asymptomatic
Women more likely to have silent infarcts
Differential diagnosis of prolonged chest pain: AMI, aortic dissection, pericarditis, esophageal problems, biliary tree, pneumothorax, pulmonary embolism, pleurisy, chest wall problems, and psychogenic

38. Arrhythmias in the first 48 hrs are due to ischemia
MR due to papillary muscle dysfuntion is seen with inferior wall MIs
VSD is seen with anterior and inferior MIs
Inferior MIs are associated with more stable arrhythmias
Anterior MIs can result with poorer prognosis associated with Mobitz II and BBBs
Both anterior and inferior MIs can result in septal wall rupture

39. Acute Coronary Syndrome (ACS)
NSTEMI(non Q wave MI)/UA: episodic cessation of coronary blood flow or vasospasms(prinzmetal’s) or drug induce, like cocaine
NSTEMI: Detectable release of biological
markers(Tnp I, T, MB isoenzymes) hours after the onset of ischemic chest pain
Unstable angina(UA): no detectable
markers released

40. STEMI(Q wave MI) most often by occlusive thrombus
Rule out other life-threatening conditions (i.e. aortic dissection, PE, tension pneumothorax, esophageal rupture, perforated ulcer)
Risk stratification-TIMI risk score
ID higher risk patients for adverse event particularly with anterior wall MIs
Cardiac marker helpful but do not delay implementation of reperfusion therapy, if not contraindicated

41. TIMI RISK SCORE PATIENTS WITH DIAGNOSIS STEMI
Prognostic variables Points
Age >75 yrs
Age 65-75yrs
DM, HTN, or angina PE
SBP <100mm Hg
HR > 100/min
Killip class II-IV
wt < 67kg (150 lb)

42. Prognostic Variables Points
Presentation
Ant. ST elevation or LBBB
Time to reperfusion > 4 hrs
Risk score = total points (0-14) correlates
30-day mortality rate (%) with 0 risk=0.8%, 5 risk=12%, and >8 risk=36%

43. Myocardial Infarction
Marker
Initial elevation
Peak elevation
Return to normal
Myoglobin
1-4 hrs.
6-7 hrs.
24 hrs.
Troponin I
3-12 hrs.
7-10 days
CKMB
20 hrs.
2-3 days
CKMB isoform
2-6 hrs.
18 hrs.
2 days
LDH
10 hrs.
1-2 days
10-14 days

44. ST elevation: Q-wave(transmural infarct) or Non Q wave subendocardial infarct)MI
Not frequently seen
Earlist changes is hyperacute or peaked T waves
ST segment elevation in leads corresponding to involved region of myocardial damage
Initially J point elevation and concave ST segments

45. Over time ST segments becomes convex or rounded upwards
ST segment indistinguishable from T waves
QRS-T complex resemble a monophasic action potential
Initial Q waves develop several hrs to days and the loss of R wave amplitude

46. Abnormal Q wave criteria:
Q waves in leads V1 to V3 or a Q wave greater than or equal 30 msec in leads I, II, aVL, aVF, or V4 to V6
Must be present in two contiguous leads and a depth greater than or equal 1mm
Overtime Ist 2 wks or several hrs after the event R wave amplitude is markly reduced
Q waves deepen

47. Overtime, several hrs or weeks after the event
R wave amplitude is markedly reduced
Q-wave deepens
T waves become inverted

48. Management of UA and NSTEMI

49. STEMI/New LBBB **PCI within 12 hrs. of CP Onset and within 90
Minutes of arrival to ED

50. STEMI/New LBBB
Consider emergent reperfusion (fibrinolytics or PCI) in ALL pts. that present with STEMI or new LBBB within 12 hrs. of onset of symptoms and who are < age 75
Fibrinolytics
LBBB benefits most
anterior>inferior (amt. of myocardium saved)
NSTEMI (not much myocardium lost), the risks of fibrinolytics outweighs the benefits
So, ONLY give fibrinolytics to STEMI or NEW LBBB or RBBB
Actually shown to increase mortality in NSTEMI

51. Medical Therapy for ACS STEMI
Fibrionolytic (reteplase, tenectaplase)
Indications: PCI unavailable
timing: <6-12 hrs
CI: ICB, chronic severe HTN, elderly
Glycoproteins IIb/IIIa inhibitors: (Abciximab)
Indications: All ACS
timing: on decision to go to cath lab
CI: CABG, coagulopathy, renal failure
Typically not given to those with UA/NSTEMI unless
PCI is anticipated
Give along with ASA & heparin in those that PCI is
likily

52. Contraindication to fibrinolytics
Absolute
Previous hemorrhagic stroke at ANY time; other CV events within one year
Intracranial neoplasm
Active internal bleeding
Suspected aortic dissection
Relative
Persistent BP>180/110
Remote CVA (>1year)
INR>2-3; bleeding problem
Recent (2-4 wks) major trauma
Non-compressible vascular puncture
Previous exposure to streptokinase/antistreplase
Pregnancy
Active peptic ulcer
Chronic HTN

53. Narcotic analgesics: (Morphine)
Indications: Severe pain
Timing: Presentation
CI: Respiratory depression
Antithrombotics: (Heparin, LMWH)
Indications: ALL ACS (except those who will receive streptokinase)
CI: thrombocytopenia, drug allergy
Heparin is required if using t-PA, r-PA, or TNK
LMWH is better in pts. with NSTEMI

54. Nitrates: sublingual, oral, IV
Indications: Angina
Timing: Presentation
CI: Hypotension
Beta-Blockers
Indications: Active ischemic symptoms and prophylaxis
Timing: On admission in CCU or ED
CI: CHF, bradycardia, asthma

55. Antiplatlets agents:(Clopidogrel, ASA)
Indication: antiplatlet unless CI
Timing: On decision to go to the cath lab
CI: Upcoming CABG Sx, coagulopathy
ACE inhibitors:
Indication: CHF,ant wall infarct, EF < 40%, pulmonary congestion, increase BP
Timing: On admission
CI: hyperkalemia, RF, hypotension

56. Statins: Supplemental oxygen: Indications: CAD Timing: On admission
CI: Myopathy, sensitivity
Supplemental oxygen:
Indications: First 6 hrs, especially patients with oxygen desaturation (< 90% by pulse ox)

57. QUESTIONS

58. QUESTIONS