Transcript Coronary Heart Disease

Coronary Heart/Artery
Disease
J.B. Handler, M.D.
Physician Assistant Program
University of New England
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Abbreviations
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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
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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
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angioplasty
Coronary Anatomy
AllRefer Health
Atherosclerosis
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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 risk
e.g. male <55; female <65.
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Risk Factors for Atherosclerosis
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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
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Elevation of CRP, an inflammatory marker
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C-reactive Protein and
Inflammation
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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.
<1 mcg/ml, 1-3 mcg/ml, >3 mcg/ml
Low risk
Intermediate risk
High risk
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Pathogenesis of Atherosclerosis:
Endothelial Dysfunction
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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
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Primary prevention: Risk factor modification smoking cessation, antihypertensive Rx, treatment
of dyslipidemia, estrogen replacement (premenopause), 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
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Emerging data using Aspirin and primary
prevention of 1st MI (men), stroke (women) and
vascular death. Physician’s 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.
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Recommendation: 75 ASA daily (optimal dose
unclear).
Must balance gain from ASA against increased
risk of bleeding.
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Prevention and Lipids
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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
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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).
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– Reversible vs permanent: dependent on how
long ischemia is present; prolonged
ischemia infarction.
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Usually accompanied by characteristic ECG
findings.
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Silent vs. Symptomatic Disease
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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)
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Prolonged O2 supply often results in unstable
angina or infarction.
– Placque rupture and thrombosis likely present
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Coronary Atherosclerosis
NYerRN
Sudden Cardiac Death
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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.
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15-20% of patients with *AMI will die
before reaching the hospital.
*Acute Myocardial Infarction
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Women are Different
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Women with CHD often misdiagnosed;
presentation often atypical:
– Atypical symptoms: Unusual pain presentations
– Pain radiating to right arm; arm pain alone
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False negative stress tests common
– Single vessel disease more common
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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
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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:
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– Xanthelasma, xanthomas- hyperlipidemia.
– Funduscopic abnormalities: A-V nicking,
hypertensive, diabetic changes.
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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 ECG’s 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 echocardiographysee 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
patient’s 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
NYerRN
Medical Treatment of Angina
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Treat or eliminate aggravating factors.
Acute attacks: Sub-lingual NTG venodilator>arterial 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:
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– Reduce mortality post MI
– Reduce mortality in patients with heart failure
(HF)
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Beta Receptor Blockers
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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 forms:
Isosorbide 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
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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
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Some Ca blockers also have negative inotropic
and chronotropic effects MVO2
Do not reduce mortality post MI (compared to ßblockers.
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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
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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)
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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
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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.
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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
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Patients with unacceptable symptoms in spite of
optimal medical Rx.
3 Vessel CAD especially with LV dysfunction
CABG
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)
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Catheter Based Techniques
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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
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Catheters used to open stenosed/occluded
coronary arteries or bypass grafts.
Angioplasty (PTCA), Atherectomy, etc.
– Problem: 30-40% re-stenosis rate.
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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 (14%) 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
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Operative mortality increased if age > 70, EF<
.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
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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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Prinzmetal’s Angina
Coronary ischemia as a result of vasospasm.
 Symptoms at rest, often in early A.M.
 Women > 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
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Unstable Angina (UA)
Myocardial Infarction:
– MI: STEMI
– MI: NSTEMI
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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
Images.google.com
Unstable Angina (UA)
Angina at rest or with minimal activity,
often lasting > 10 min. (without MI
negative cardiac markers).
 New onset angina (< 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
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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
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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
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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
NYerRN
Acute Myocardial Infarction
Statistics: > 1.1 million events/yr. in U.S.
Death in >350,000 (half are sudden)
>750,000 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
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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:
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– CK MB fraction: Heart – nl <4% of total CK
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Serum Markers
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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 >
0.05ng/mL; diagnostic for MI with high
sensitivity/specificity if > 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
Management of MI
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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
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Indications: ST elevation of >1 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 (PVC’s, VT,
AIVR)
 Rapid evolution of ECG (often to Q waves)
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Post -Thrombolytic Management
10-20% of infarct related vessels will reocclude 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:
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– Open artery within 3 hours of onset of
symptoms (includes transportation).
– Open artery within 90” after presenting to
hospital that does PCI/angioplasty/stenting.
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Requires capability of CABG if necessary.
*PCI- percutaneous coronary intervention
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Acute Primary PTCA
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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
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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
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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
NYerRN
NonSTEMI
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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.
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– HOPE trial – ACEI in patients with LV
dysfunction post MI –mortality 20%.
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Statins to LDL <??? (see Dyslipidemias).
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Post Infarction Management
(IO)
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In hospital mortality 10-15% determined by size
of the infarct.
Patients at increased risk post MI:
Recurrent ischemic pain
NonSTEMI infarct
CHF
LVEF < .40
Stress test (low level) induced ischemia
High 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………
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