CORONARY ARTERY DISEASE/MI

By Henri Godbold MD

Med Peds

Noon Conference 9/21/2006

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

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

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

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)

ASSOCIATED SYMPTOMS

• Dyspnea

• Diaphoresis

• Dizziness

• Syncope

• Palpations

• Deep breathing pain

• Nausea and vomiting• Edema• Orthropnea• Paroxysmal nocturnal

dyspnea• Positional pain

CARDIAC RISK FACTORS

OTHER• Hx CVA and PVD

disease

Absolute - FH- smoking- DM- HTN - Hyperlipidemia (LDL> 130, HDL<35)- AGE

(men>45,Female>55)

Relative• Obesity• sedentary life• stress • postmenopausal state

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

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

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

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

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

• Correct reversible risk factors: smoking, hypertension, uncontrolled DM, obesity, stress, life style modification

• Risk Stratification (Table 27.4)

CAD Risk Association with Lipoprotein Cholesterol Abnormalities

Lipoprotein cholesterol

Levels (mg/dl) Estimated

CHD Risk

LDL <130 low

130-159 moderate

>160 high

HDL >65(chol/HDL ratio >4.5) low

<35(chol/HDL ratio <4.5) Mod-high

VLDL 50-100(or fasting TG 250-500) low

>100(or fasting TG >500) ? high

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

• Intermediate (10%-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

TESTING MODALITIESCardiac 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

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

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

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

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)

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

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

PCI

• 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

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

• 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

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

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

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

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

Fibrates(Gemfibrozil and Fenofibrate)

• Not first-line

• Decreases VLDL synthesis enhancing clearance

• Raises HDL cholesterol

• Well tolerated except in combo w/ statins possible rhabdomyolysis

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

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

• 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 160-190mg/dl

• 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

• Primary 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

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

• 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

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

• 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

TIMI RISK SCORE PATIENTS WITH DIAGNOSIS STEMI

• Prognostic variables Points Age >75 yrs 3 Age 65-75yrs 2 DM, HTN, or angina 1• PE SBP <100mm Hg 3 HR > 100/min 2 Killip class II-IV 2 wt < 67kg (150 lb) 1

• Prognostic Variables Points

Presentation

Ant. ST elevation or LBBB 1

Time to reperfusion > 4 hrs 1

Risk score = total points (0-14) correlates

30-day mortality rate (%) with 0 risk=0.8%, 5 risk=12%, and >8 risk=36%

Myocardial Infarction

Marker Initial elevation

Peak elevation

Return to normal

Myoglobin 1-4 hrs. 6-7 hrs. 24 hrs.

Troponin I 3-12 hrs. 24 hrs. 7-10 days

CKMB 3-12 hrs. 20 hrs. 2-3 days

CKMB isoform

2-6 hrs. 18 hrs. 2 days

LDH 10 hrs. 1-2 days 10-14 days

• 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

- 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

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

Overtime, several hrs or weeks after the

event– R wave amplitude is markedly reduced– Q-wave deepens– T waves become inverted

Management of UA and NSTEMI

STEMI/New LBBB

P C I

F ib rin o lytic th e ra pyif n o t con tra in d ica ted

a n d if P C I n o tim m ediately a va ila b le

S T E M I o r N e w L B B BG ive A S A , b e ta b lo cke rs,

n itra te s p rn , G P IIb /IIIa , U HFo r L M W H & m o n ito r rh ythm

**PCI within12 hrs. of CPOnset and within 90Minutes of arrival to ED

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

RBBBActually shown to increase mortality in NSTEMI

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

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

• Narcotic analgesics: (Morphine)– Indications: Severe pain– Timing: Presentation– CI: Respiratory depression

• Antithrombotics: (Heparin, LMWH)– Indications: ALL ACS (except those who will receive

streptokinase)– Timing: Presentation– CI: thrombocytopenia, drug allergy– Heparin is required if using t-PA, r-PA, or TNK– LMWH is better in pts. with NSTEMI

• 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

• 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

• Statins:– Indications: CAD– Timing: On admission– CI: Myopathy, sensitivity

• Supplemental oxygen:– Indications: First 6 hrs, especially patients

with oxygen desaturation (< 90% by pulse ox)

QUESTIONS

QUESTIONS