Coronary%20Heart/Artery%20Disease

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Coronary Heart/Artery Disease

• J.B. Handler, M.D.
• Physician Assistant Program
• University of New England

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Abbreviations

• CHD- coronary heart disease
• LDL- low density lipoprotein
• HDL- high density lipoprotein
• HTN- hypertension
• CAD- coronary artery disease
• PVR- peripheral vascular resistance
• HCM- hypertrophic cardiomyopathy
• EF- ejection fraction
• PCI- percutaneous coronary intervention
• CHO- carbohydrate
• SVR systemic vascular resistance (same as PVR)
• HF- heart failure

• CO- cardiac output
• CK- creatine kinase (also CPK)
• AIVR- accelerated idioventricular rhythm
• VT- ventricular tachycardia
• ACEI- angiotensin converting enzyme inhibitor
• T-PA- tissue plasminogen activator
• UF- unfractionated (heparin)
• STEMI- ST segment elevation MI vs NonSTEMI
• PAD- peripheral arterial disease
• PTCA- percutaneous transluminal coronary
  angioplasty

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Coronary Anatomy
AllRefer Health
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Atherosclerosis

• Leading cause of cardiovascular disability and
  death in the U.S. More than 12 million persons
  have CHD and sequelae ?500,000 deaths/yr
• Gradual process involving the 3 major coronary
  arteries and their branches focal involvement.
• Gradual reduction of arterial lumen resulting in
  ischemia due to reduced O2/blood supply.
• Abrupt arterial occlusion/thrombosis initiates
  MI.

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Coronary Atherosclerosis
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Risk Factors for Atherosclerosis

• Lipids Total Cholesterol, LDL, HDL,
  triglycerides
• Hypertension
• Cigarette smoking
• Diabetes Mellitus
• Family history for CAD- 1st degree relative-
  younger the onset, higher the riske.g. male lt55
  female lt65.

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Risk Factors for Atherosclerosis

• Male gender
• Age (men? 45 women ?55)
• Hypoestrogenemia
• Physical inactivity
• Central obesity
• Elevated plasma homocysteine levels
• Amino acid derived from digestion of meat and
  dairy proteins
• Elevation of CRP, an inflammatory marker

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C-reactive Protein and Inflammation

• A marker of chronic inflammation
• Independent risk factor for CHD if elevated, even
  in patients with normal LDL-C.
• Inflammation is likely a component of the
  atherosclerotic process
• Chronic inflammation may be involved in the
  development of placque rupture and unstable
  coronary lesions.
• lt1 mcg/ml, 1-3 mcg/ml, gt3 mcg/ml

Intermediate risk
Low risk
High risk
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Pathogenesis of Atherosclerosis Endothelial
Dysfunction

• Chemical causes LDL, homocysteine, glucose.
• Hemodynamic- disturbed flow patterns,
  hypertension.
• Biological- ??viral, endotoxin, immune complexes.
• Nitric Oxide (NO) made by endothelial cells is
  protective vasodilator with anti-atherosclerotic
  properties- decreased or absent production in
  presence of smoking, HTN and diabetes.

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Prevention of Atherosclerosis

• Primary prevention Risk factor modification -
  smoking cessation, antihypertensive Rx, treatment
  of dyslipidemia, estrogen replacement
  (pre-menopause), glucose regulation/DM, regular
  exercise, aspirin prophylaxis in high risk
  groups.
• Secondary prevention Delay or abort disease
  progression in patients with documented CHD more
  aggressive risk factor modification.

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Aspirin and Primary Prevention

• Emerging data using Aspirin and primary
  prevention of 1st MI (men), stroke (women) and
  vascular death. Physicians Health Study data.
• At risk Men age 45-79 or women age 55-79 with 2
  or more of the following risk factors Smoking,
  HTN, hypercholesterolemia, FH.
• Diabetes ASA for all adult diabetics with ? 1
  other CV risk factor.
• Recommendation 75 ASA daily (optimal dose
  unclear).
• Must balance gain from ASA against increased risk
  of bleeding.

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Prevention and Lipids

• Increased LDL increases risk of CAD, stroke and
  PAD.
• Aggressive treatment can prevent coronary events
  and stroke in patients without clinically
  manifest disease (see lecture on dyslipidemias).
• Secondary prevention aggressive LDL lowering
  decreases progression and subsequent events in
  patients with documented atherosclerosis.
• Disease regression unlikely, reported
  occasionally.

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Coronary Artery/Heart Disease
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Myocardial Ischemia

• Coronary stenosis once significant, results in
  imbalance between blood supply and demand. This
  limits the normal increase in perfusion when
  there is increased demand (activity, exercise).
• Contributory factors ? myocardial O2 demand
• Significant LVH, aortic stenosis)
• Tachyarrhythmias (rapid Afib or flutter, others).

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Effects of Active Ischemia

• Symptoms usually present (below) but not always.
• Cardiac Mechanical, electrical and valvular
  dysfunction (mitral regurgitation).
• Reversible vs permanent dependent on how long
  ischemia is present prolonged ischemia?
  infarction.
• Usually accompanied by characteristic ECG
  findings.

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Silent vs. Symptomatic Disease

• Long asymptomatic stage before symptoms.
• Symptoms of reversible ischemia (angina pectoris)
  occur as a result of
• Increased myocardial O2 demand in the presence of
  fixed stenosis (?supply)
• Reversible decrease of O2 supply vasospasm?
  significant narrowing (with or without
  atherosclerosis)
• Prolonged ?O2 supply often results in unstable
  angina or infarction.
• Placque rupture and thrombosis likely present

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Coronary Atherosclerosis
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Sudden Cardiac Death

• Death within 1 hour after onset of symptoms
  usually within minutes. Malignant arrhythmia
  commonly present.
• Common presenting manifestation of CHD.
• Frequent end point in patients with CHD, prior MI
  and impaired LV function.
• 15-20 of patients with AMI will die before
  reaching the hospital.

Acute Myocardial Infarction
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Women are Different

• Women with CHD often misdiagnosed presentation
  often atypical
• Atypical symptoms Unusual pain presentations
• Pain radiating to right arm arm pain alone
• False negative stress tests common
• Single vessel disease more common
• Elderly or diabetic women may complain of
  general malaise, loss of appetite, vague
  abdominal discomfort if risk factors?get ECG!
• Need higher index of suspicion in women with risk
  factors.

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Stable Angina Pectoris

• Chest discomfort- heaviness, tightness, pressure,
  squeezing, burning, aching or choking may not be
  described as pain.
• Levine sign substernal or to left of sternum.
• Crescendo-decrescendo pattern, 1-5 min.
• Radiation left shoulder and upper arm, back,
  neck, jaw and teeth.

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Precipitating Factors

• Exertion, exercise, emotional duress, cold
  weather, sexual activity, cigarette smoke, large
  meals.
• Patterns Often reproducible with activity
  patterns may vary depending on time of day,
  coronary tone threshold lower in a.m. and after
  emotional duress.
• Sx resolve with cessation of activity, relaxation
  and following sub-lingual (rapid acting) NTG.

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Clinical Presentation

• Characteristic history
• Presence of risk factors
• PE often normal in between episodes may include
  
• Xanthelasma, xanthomas- hyperlipidemia.
• Funduscopic abnormalities A-V nicking,
  hypertensive, diabetic changes.
• Cardiac- S4 gallop (during angina), bruits
  (atherosclerosis), murmurs, changes in BP.

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Xanthelasma
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Electrocardiogram

• Often normal in between anginal episodes. May
  show prior infarcts, ST-T changes.
• During episode may show characteristic ischemic
  changes ST segment depression and/or T wave
  changes changes normalize within minutes
  following an anginal episode.

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Stress Electrocardiography

• Most useful non-invasive procedure for evaluating
  the patient with angina.
• Standardized protocols utilizing exercise or
  medications are used to increase cardiac workload
  (or coronary blood flow)- see lecture on cardiac
  testing.
• Resting and stress ECGs are compared looking for
  characteristic changes of ischemia.

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Stress Electrocardiography
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Ischemia
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Stress Testing

• Sensitivity/Specificity Influenced by number of
  involved vessels, duration of exercise, and
  presence of resting ECG abnormalities.
• Sensitivity/Specificity can be improved by adding
  imaging techniques Myocardial perfusion
  scintigraphy or echocardiography- see lecture on
  cardiac testing.

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Coronary Arteriography

• The gold standard for assessing severity of
  CAD. Defines vessels involved, degree of
  stenosis and LV function.
• Angiography is used in conjunction with patients
  symptoms and extent of ischemia (via stress
  testing) to determine severity and significance
  of disease, and is often the final piece of
  information necessary to determine therapeutic
  options.

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Angiogram Coronary Stenosis
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Angiogram of Stenosis in Graft
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Medical Treatment of Angina

• Treat or eliminate aggravating factors.
• Acute attacks Sub-lingual NTG -
  venodilatorgtarterial dilator. Reduces LV volume
  (preload) decreasing O2 consumption may improve
  collateral flow also aborts coronary vasospasm.
  Usual dose is 0.3-0.6 mg, and repeated at 3 to 5
  minute intervals.
• Prophylactic sub-lingual NTG taken 5 minutes
  before activities likely to precipitate angina.

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Beta Receptor Blockers

• Prevent angina by decreasing myocardial O2
  consumption (MVO2) decrease HR, contractility
  and BP. Improve exercise tolerance and reduce
  symptoms.
• Other benefits of ß-blockers
• Reduce mortality post MI
• Reduce mortality in patients with heart failure
  (HF)

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Beta Receptor Blockers

• Can induce bronchospasm in patients with asthma
  or COPD Role for ß-1 selective agents.
• Numerous ß-blockers available. Choice may be
  influenced by selectivity and other features.
  Widely used in Rx of HTN, arrhythmias, HF,
  essential tremor and prevention of migraine
  headaches.
• Propranolol, Atenolol, Metoprolol, Carvedilol, et
  al.

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Long Acting Nitrates

• Long acting nitrates- Oral, topical
  formsIsosorbide dinitrate or mononitrate
  (oral)NTG ointment or patches (topical).
• Used to prevent angina- ?MVO2 improve exercise
  tolerance.
• Tolerance - need for nitrate free intervals.
• Side effects headaches, hypotension.
• Must DC Viagra when using nitrates!

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Calcium Channel Blockers

• Decrease myocardial O2 requirements by dilating
  peripheral arteries/arterioles, reducing BP, LV
  wall stress, and afterload also reduce coronary
  tone and spasm- induce vasodilation.
• Result is ?MVO2 (myocardial O2 consumption)
• Improve exercise tolerance/prevent angina
• Some Ca blockers also have negative inotropic and
  chronotropic effects? ?MVO2
• Do not reduce mortality post MI (compared to
  ß-blockers.

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Dihydropyridine Ca Blockers

• Dilate arterioles, ?PVR? afterload ? MVO2 Minimal
  negative inotropic and chronotropic effects.
• Best used in addition to ?-blockers in the
  treatment of angina.
• Long acting preparations reduce likelihood of
  hypotension.
• Numerous available Nifedipine, amlodipine, and
  others.

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Diltiazem and Verapamil

• Useful as an adjunct to nitrates in the treatment
  of angina (vs ?-blocker).
• Dilate arterioles ?HR and contractility ?
  ?MVO2.
• Diltiazem can be used cautiously with ?-blocking
  agents in treatment of angina- avoid Verapamil.
• Both are also useful in hypertension and for
  certain cardiac arrhythmias.
• Avoid in patients with heart failure.

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Ranolazine (Interest Only)

• New (2006) for treatment of chronic angina in
  patients without adequate response to standard
  meds (above) modest improvement in Sx.
• Unique MOA ?s late Na current, ?ing intracelular
  calcium. Also decreases fatty acid
  metabolism,?ing CHO metabolism which takes less
  energy/O2.
• No significant effect on HR or BP.
• Side effects Dizziness, HA, constipation and
  nausea.
• ECG Increases Q-T interval caution.

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Anti-Platelet Agents

• Low dose aspirin (81-325 mgs.) has been shown to
  reduce coronary events post myocardial
  infarction. Indications all pts with CHD.
• ?s incidence of subsequent MI, cardiac death.
• Clopidogrel inhibits ADP-induced platelet
  aggregation option if ASA is contraindicated.
• ASA or Clopridogrel also recommmended in patients
  with PAD and carotid disease.
• ?s incidence of subsequent MI, cardiac death,
  stroke.

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Revascularization Indications

• Patients with unacceptable symptoms in spite of
  optimal medical Rx.
• 3 Vessel CAD especially with LV dysfunction
• Left main or left main equivalent disease
• Following treatment of unstable angina if there
  is evidence of early onset ischemia.
• Patients post MI with ongoing ischemia, or with
  early onset ischemia via stress testing.
• Acute MI (see below)

CABG
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Catheter Based Techniques

• Angioplasty and related techniques can be
  performed with low morbidity, mortality, and
  rapid recovery.
• Indicated primarily for single or 2 vessel
  disease.
• Comparable mortality and infarction rates
  compared to CABG over 1st three years, but high
  rate of repeat procedures until recently.
• Major drawback Restenosis requiring
  repeat/multiple procedures? improved last 5 yrs
  with newer drug eluting stents (below).

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Catheter Based Techniques

• Catheters used to open stenosed/occluded coronary
  arteries or bypass grafts.
• Angioplasty (PTCA), Atherectomy, etc.
• Problem 30-40 re-stenosis rate.
• Stent Placement- insertion of metal sleeve into
  stenosis ?re-stenosis-15-20
• Using drug eluting (Sirolimus, Paclitaxel) stents
  ??s re-stenosis- 5-8 problems with late stent
  thrombosis ? intense anti-platelet Rx..

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Coronary Angioplasty
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Coronary Angioplasty and Stent
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Stent Placement
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Coronary Artery Bypass Surgery

• Obstructed coronary arteries are bypassed using
  veins or arteries. Low mortality (1-4) if LV
  function preserved.
• Best long term results of patency and flow.
• Saphenous veins, radial artery and internal
  mammary arteries are commonly used to bypass
  diseased segments.

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Coronary Bypass Graft Surgery
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Coronary Artery Bypass Surgery

• Operative mortality increased if age gt 70, EFlt
  .35.
• Vein closure rates 10-20 in 1st year, then 4
  annually vein grafts and native vessels subject
  to recurrent disease.
• Internal mammary grafts-high patency rate over
  time- best option for grafts where possible.
• Radial artery grafts are better than vein grafts,
  but use is limited.

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Coronary Vasospasm

• May present in patients with normal coronaries,
  or superimposed on atherosclerotic disease.
• Often induced by exposure to cold, emotional
  stress, meds (ergot), or drugs (cocaine).
• Clinical presentation Chest discomfort
  accompanied by ST segment elevation and
  arrhythmias.
• May progress to MI (and consequences) if spasm
  does not resolve.

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Prinzmetals Angina

• Coronary ischemia as a result of vasospasm.
• Symptoms at rest, often in early A.M.
• Women gt men. AKA variant angina.
• Coronary arteriography often identifies normal
  appearing vessels- vasospasm can be induced
  pharmacologically in cardiac cath lab.
• Treatment very successful with nitrates and
  calcium channel blockers.

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Acute Coronary Syndromes

• Unstable Angina (UA)
• Myocardial Infarction
• MI STEMI
• MI NSTEMI
• There is considerable overlap between UA and
  NSTEMI. The pathology is nearly identical. The
  major difference with NSTEMI there are abnormal
  cardiac markers (CK MB or troponins) that
  indicate cell necrosis. With UA, no cell
  necrosis has occurred (yet).

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Plaque Rupture
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Unstable Angina (UA)

• Angina at rest or with minimal activity, often
  lasting gt 10 min. (without MI? negative cardiac
  markers).
• New onset angina (lt 4 wks) with progressive
  symptoms? more severe pain.
• Accelerating or creshendo angina in patient with
  previously stable angina.
• 50 of patients will have abnormal ECG (St
  depression and T wave inversion).

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Characteristics Unstable Angina

• Pathology complex coronary lesions- stenosis
  with placque rupture, hemorrhage, thrombus.
• Prognosis (untreated) High risk of developing MI
  in following days/weeks.
• ECG evidence of ischemia- ST depression, TW
  inversion LV dysfunction common during ischemia
  (echo imaging).
• No elevation of cardiac markers/enzymes.
• Presentation of Non-STEMI infarct often
  indistinguishable from unstable angina (but
  enzymes/markers are elevated with NSTEMI).

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Treatment Unstable Angina

• Hospitalize, bedrest, O2, monitoring.
• Full anticoagulation anti-platelet therapy
  Heparin (UF Heparin or LMW) plus ASA plus
  Clopidogrel other anti-platelet agents (IV
  glycoprotein IIb/IIIa antagonists- (eptifabatide,
  tirofiban) should be added in highest risk
  patients and before PCI.
• Nitrates (topical, IV), ?-blockers, and
  Ca-blockers commonly used to ?MVO2.

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Outcomes with Unstable Angina

• 20 remain unstable and require invasive
  evaluation and revascularization.
• 80 improve medically. Once stable, some form of
  stress testing is performed. An early test is
  an indication for invasive evaluation and
  revascularization based on the anatomy.

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Acute Myocardial Infarction

• Definition Prolonged ischemia resulting from
  inadequate tissue perfusion leading to tissue
  necrosis and myocardial cell death.
• Includes ST segment elevation MI and non-ST
  segment elevation MI.
• STEMI CAD?Placque rupture? Platelets?Clotting ?
  Occlusive Thrombus.
• Inflammation contributes to placque
  rupture/thrombosis.

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CAD with Thrombus
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Acute Myocardial Infarction

• Statistics gt 1.1 million events/yr. in U.S.
  Death in gt350,000 (half are sudden) gt750,000
  hospitalizations/yr.
• Infarct location and size correlates with
  distribution of occluded vessel, collateral
  circulation, and presence of additional disease.

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Clinical Presentation

• Often in early A.M hours.
• 1/3 with premonitory history of unstable angina
• Chest pain much more severe than angina atypical
  presentations.
• Patients are anxious, restless, diaphoretic and
  in distress.
• LV dysfunction or stiffness can result in SOB.
• Painless infarction common in diabetics.

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Physical Findings

• Pulse and BP variable and change frequently
  hemodynamic instability common.
• Irregularities in pulse may represent
  arrhythmias.
• Lungs usually clear unless heart failure present.

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Physical Findings

• S4 gallop in most S3 unusual unless CHF.
• Transient apical mitral regurgitant murmurs
  usually represent papillary muscle dysfunction.
• Extremities cyanosis/cold indicate low CO.

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Serum Markers

• Enzymes and proteins released from necrotic
  myocardial cells.
• CK (creatine kinase) enzyme released from damaged
  skeletal muscle and heart. Total CK (aka CPK)
  always elevated with MI. Isoenzymes distinguish
  between source
• CK MB fraction Heart nl lt4 of total CK

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Serum Markers

• CK MB isoenzymes rise within 4-6 hrs, peak in
  16-24 hrs (2-10x nl), fall to baseline in 2-3
  days.
• Cardiac specific troponins cTnI ( cTnT) rises
  within 4-6 hours, peak in 8-12 hours and remains
  elevated for 5- 7 days. Somewhat more
  sensitive/specific for small MI. Also useful if
  symptoms are several days old. Abnormal if gt
  0.05ng/mL diagnostic for MI with high
  sensitivity/specificity if gt 0.1ng/mL

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Lab and Other Findings

• Leukocytosis common.
• ECG Diagnostic criterion for STEMI vs. NonSTEMI
  (see ECG lectures).
• CXR often normal, unless there is HF or prior
  cardiac problems.
• Echocardiography Provides bedside assessment of
  global and regional LV function. Identifies
  Mitral regurg if present.

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ECG Acute Anterior MI
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Myocardial Infarction
NYerRN
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Management of MI

• Pre-hospital care management of electrical and
  hemodynamic instability race against time O2,
  analgesia, other meds as indicated.
• Parenteral narcotics Morphine sulfate
• Aspirin given early in ED
• Nitroglycerin usually initiated IV and
  titrated.to pain and BP.
• IV followed by oral ?-blockers- decrease MVO2,
  reduce in hospital and post discharge mortality.

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Thrombolytic Therapy STEMI

• Indications ST elevation of gt1 mm. in two or
  more contiguous/adjacent leads. Not indicated
  with ST depression or TW inversion alone.
• Goal Reduced mortality and infarct size.
• Greatest benefits with large infarcts and when
  given within the first 1-3 hrs of symptoms (50
  reduction in mortality).
• Contraindications uncontrolled HTN, prior stroke
  (within one year) or cerebral hemorrhage, known
  bleeding diathesis, recent head trauma.

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Thrombolytic Therapy STEMI

• Relative contraindications recent (within 3
  weeks) abdominal or thoracic surgery.
• Agents Recombinant t-PA (Alteplase), Reteplase,
  Tenecteplase. All given by IV injection or
  infusion? similar efficacy.
• Risks Bleeding and intracerebral hemorrhage.

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Post -Thrombolytic Management

• Includes ASA (ongoing) and Heparin (x 24 hours).
  Clopidogrel often given as well.
• Rapid resolution of pain
• Ventricular arrhythmias (PVCs, VT, AIVR)
• Rapid evolution of ECG (often to Q waves)

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Post -Thrombolytic Management

• 10-20 of infarct related vessels will re-occlude
  during the hospitalization- recurrent pain and
  ECG changes indication for catheterization and
  revascularization.
• Stable patients post reperfusion stress testing
  prior to discharge.

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Acute Primary PCI

• Available in a few centers-alternative to
  thrombolytic therapy with better results.
• Patients taken from ED directly to cath lab for
  acute angioplasty/stenting. Goals
• Open artery within 3 hours of onset of symptoms
  (includes transportation).
• Open artery within 90 after presenting to
  hospital that does PCI/angioplasty/stenting.
• Requires capability of CABG if necessary.

PCI- percutaneous coronary intervention
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Acute Primary PTCA

• More effective than thrombolytics in opening
  occluded arteries improved outcomes.
• An alternative approach if thrombolysis
  contraindicated. Preferred in elderly patients.
• Lower risk of hemorrhage.
• If within 1.5 hours of hospital that does acute
  angioplasty (with rapid response rate), think
  about transfer rather than thrombolytics.

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Hospital Phase Care

• CCU care
• B-blockers, nitrates, aspirin/clopidogrel as
  tolerated.
• ACE Inhibitors Improve short and long term
  survival and aid in LV remodeling post
  MI.Beneficial with large infarcts complicated by
  significant LV dysfunction, low EF or CHF.
• Aldosterone blockers patients with large MI,
  ?EF or symptoms of heart failure.

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Complications of Acute MI

• Arrhythmias atrial and ventricular.
• Left ventricular dysfunction CHF-primary cause
  of intra-hospital death.
• Papillary muscle dysfunction Mitral
  Regurgitation- new murmur
• Hypotension and shock
• RV infarction
• Conduction abnormalities
• Ventricular aneurysm formation

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Ventricular Aneurysm
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NonSTEMI

• Infarcts characterized by by prolonged ischemia,
  small elevations of cardiac markers and EKG
  changes showing ST depression and/or T wave
  inversions.
• CAD?Placque rupture?Platelets?Clotting ?
  Thrombus. Similar Rx as Unstable Angina.
• Considered incomplete infarcts with lower
  initial mortality but high risk of re-infarction
  and with high mortality.
• Very aggressive management often involving
  angiography and revascularization.

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Uncomplicated Infarction

• Pre-discharge low level stress test with maximal
  stress test 6 wks. post discharge.
• Cardiac Rehabilitation
• Aggressive risk factor modification
• Use of B-blocking agents and ACE Inhibitors.
• HOPE trial ACEI in patients with LV dysfunction
  post MI mortality ?20.
• Statins to ?LDL lt??? (see Dyslipidemias).

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Post Infarction Management (IO)

• In hospital mortality 10-15 determined by size
  of the infarct.
• Patients at increased risk post MIRecurrent
  ischemic painNonSTEMI infarctCHFLVEF lt
  .40Stress test (low level) induced ischemiaHigh
  grade ventricular arrhythmias late in course
• Invasive evaluation and revascularization.

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Revascularization Post MI (IO)

• Recurrent ischemia post thrombolysis.
• Recurrent ischemia post infarct.
• LV dysfunction with ongoing ischemia.
• Patients with markedly positive stress tests and
  multi-vessel disease.
• And others