MINISTRY OF HEALTH OF UKRAINE

KHARKIV NATIONAL MEDICAL UNIVERSITY

DEPARTMENT OF INTERNAL MEDICINE 1 AND CLINICAL
PHARMACOLOGY

GUIDELINES FOR STUDENTS

ACADEMIC
INTERNAL MEDICINE
DISCIPLINE
CONTENTS MODULE #3 CURRENT PRACTICE OF INTERNAL
MEDICINE

Topic

MANAGEMENT OF PATIENTS WITH ACUTE

CORONARY SYNDROME

Author

Yuliya Shaposhnikova

Course

6 th

Faculty

Faculty of the foreign students education

APPROVED
Academic Council of HNMU
Protocol number_____
from
__________________2010

KHARKIV
HNMU 2010

ACUTE CORONARY SYNDROMES

Acute coronary syndromes (ACS) is a term used to describe a group of conditions resulting from
acute myocardial ischemia (insufficient blood flow to heart muscle) and ranging from unstable angina
(increasing, unpredictable chest pain) to myocardial infarction (heart attack). The conditions are related to
varying degrees of narrowing or blockage of single or multiple coronary arteries that provide blood,
oxygen, and nutrients to the heart. This life-threatening disorder is a major cause of emergency medical
care and hospitalization.
Acute Coronary Syndrome (ACS) is a term that encompasses a spectrum of conditions including
unstable angina (UA), the closely related condition non-ST-segment elevation myocardial infarction
(NSTEMI), and ST segment elevation myocardial infarction (STEMI).
In general, ACS is caused by an imbalance between myocardial oxygen supply and demand. Most
often, ACS is the result of decreased myocardial perfusion that results from coronary artery narrowing
caused by atherosclerotic plaque and thrombi formation involved in coronary heart disease.
When patients report anginal chest pain, the goal is to immediately classify them into one of three
groups based on their symptoms, ECG findings, and laboratory tests. These determine if the patient is
having stable angina, unstable angina, NSTEMI or STEMI.
Acute myocardial infarction (AMI) and unstable angina are part of a spectrum known as the acute
coronary syndromes (ACS), which have in common a ruptured atheromatous plaque. Plaque rupture
results in platelet activation, adhesion, and aggregation, leading to partial or total occlusion of the artery.
These syndromes include ST-segment elevation MI, non-ST-segment elevation MI, and unstable
angina. The ECG presentation of ACS includes ST-segment elevation infarction, ST-segment depression
(including nonQ-wave MI and unstable angina), and nondiagnostic ST-segment and T-wave
abnormalities. Patients with ST-segment elevation MI require immediate reperfusion, mechanically or
pharmacologically.
Clinical evaluation of chest pain and acute coronary syndromes
History. Chest pain is present in 69% of patients with AMI. The pain may be characterized as a
constricting or squeezing sensation in the chest. Pain can radiate to the upper abdomen, back, either arm,
either shoulder, neck, or jaw. Atypical pain presentations in AMI include pleuritic, sharp or burning chest
pain. Dyspnea, nausea, vomiting, palpitations, or syncope may be the only complaints.
Clinical presentation. The clinical presentation of acute coronary syndromes encompasses a wide
variety of symptoms. The classic features of typical ischemic cardiac pain are well known and will not be
further described here. Traditionally, several clinical presentations have been distinguished: prolonged
(>20 min) anginal pain at rest, new onset (de novo) severe (Class III of the Canadian Cardiovascular
Society Classification) angina, or recent destabilization of previously stable angina with at least CCS III
angina characteristics (crescendo angina). Prolonged pain is observed in 80% of patients while de novo or
accelerated angina is observed in only 20%.
However, atypical presentations of acute coronary syndromes are not uncommon. They are often
observed in younger (2540 years) and older (>75 years) patients, diabetic patients, and in women.
Atypical presentations of unstable angina include pain that occurs predominantly at rest, epigastric pain,
recent onset indigestion, stabbing chest pain, chest pain with some pleuritic features, or increasing
dyspnoea. In addition, variant angina, which forms part of the spectrum of unstable angina, may not be
recognized at initial presentation

Cardiac risk factors include age (male >45 years, female >55 years), hypertension,
hyperlipidemia, diabetes, smoking, and a strong family history (coronary artery disease in early or midadulthood in a firstdegree relative), low HDL.
Physical examination. Physical examination is most often normal, including chest examination,
auscultation, and measurement of heart rate and blood pressure. The purpose of the examination is to
exclude non-cardiac causes of chest pain, non-ischaemic cardiac disorders (pericarditis, valvular disease),
potential precipitating extra-cardiac causes, pneumothorax, and finally, to look for signs of potential
haemodynamic instability and left ventricular dysfunction. Physical examination may reveal tachycardia
or bradycardia, hyper- or hypotension, or tachypnea. Inspiratory rales and an S 3 gallop are associated with
left-sided failure. Jugulovenous distention (JVD), hepatojugular reflux, and peripheral edema suggest
right-sided failure. A systolic murmur may indicate ischemic mitral regurgitation or ventricular septal
defect.
Laboratory evaluation of chest pain and acute coronary syndromes
Electrocardiogram (ECG)
1. Significant ST-segment elevation is defined as 0.10 mV or more measured 0.02 second after the
J point in two contiguous leads, from the following combinations: (1) leads II, III, or aVF (inferior
infarction), (2) leads V1 through V6 (anterior or anterolateral infarction), or (3) leads I and aVL (lateral
infarction). Abnormal Q waves usually develop within 8 to 12 up to 24 to 48 hours after the onset of
symptoms. Abnormal Q waves are at least 30 msec wide and 0.20 mV deep in at least two leads.
2. A new left bundle branch block with acute, severe chest pain should be managed as acute
myocardial infarction pending cardiac marker analysis. It is usually not possible to definitively diagnose
acute myocardial infarction by the ECG alone in the setting of left bundle branch block.
Laboratory markers
1. Creatine phosphokinase (CPK) enzyme is found in the brain, muscle, and heart. The
cardiacspecific dimer, CK-MB, however, is present almost exclusively in myocardium.
2. CK-MB subunits. Subunits of CK, CK-MB, - MM, and -BB, are markers associated with a
release into the blood from damaged cells. Elevated CK-MB enzyme levels are observed in the serum 2-6
hours after MI, but may not be detected until up to 12 hours after the onset of symptoms.
3. Cardiac-specific troponin T (cTnT) is a qualitative assay and cardiac troponin I (cTnI) is a
quantitative assay. The cTnT level remains elevated in serum up to 14 days and cTnI for 3-7 days after
infarction.
4. Myoglobin is the first cardiac enzyme to be released. It appears earlier but is less specific for
MI than other markers. Myoglobin is most useful for ruling out myocardial infarction in the first few
hours.
Table 1.
Common Markers for Acute Myocardial Infarction
Marker
Myoglobin
CTnl
CTnT
CKMB
CKMBiso

Initial elevation after Mean time to peak Time to

MI
elevations
baseline
1-4 h
6-7 h
18-24 h
3-12 h
10-24 h
3-10 d
3-12 h
12-48 h
5-14 d
4-12 h
10-24 h
48-72 h
2-6 h
12 h
38 h

Differential diagnosis of severe or prolonged chest pain:

return

to

Myocardial infarction
Unstable angina
Aortic dissection
Gastrointestinal disease (esophagitis, esophageal spasm, peptic ulcer disease, biliary colic,
pancreatitis)
Pericarditis
Chest-wall pain (musculoskeletal or neurologic)
Pulmonary disease (pulmonary embolism, pneumonia, pleurisy, pneumothorax)
Psychogenic hyperventilation syndrome
Table 2.
Differential diagnosis of acute MI

Life-threatening

Aortic dissection
Pulmonary embolus
Perforating ulcer

Tension pneumothorax
Boerhaave syndrome
(esophageal rupture with
mediastinitis)
Other cardiovascular and Pericarditis
LV hypertrophy with strain
non-ischemic
Atypical angina
Brugada syndrome
Early repolarization
Myocarditis
Wolff-Parkinson-White syndrome Hyperkalemia
Deeply
inverted
T-waves Bundle-branch blocks
suggestive of a central nervous Vasospastic angina
system
lesion
or
apical Hypertrophic cardiomyopathy
hypertrophic cardiomyopathy
Other noncardiac
Gastroesophageal reflux (GERD) Biliary or pancreatic pain
and spasm
Cervical disc or neuropathic
Chest-wall pain
pain
Pleurisy
Somatization and psychogenic
Peptic ulcer disease
pain disorder
Panic attack

Table 3.
Therapy for Non-ST Segment myocardial infarction and unstable angina
Treatment
Antiplatelet agent
Nitrates

Beta-blocker

Heparin

Recommendations
Aspirin, 325 mg (chewable)
Sublingual nitroglycerin (Nitrostat), one tablet every 5 min for total
of three tablets initially, followed by IV form (Nitro-Bid IV, Tridil) if
needed

IV therapy recommended for prompt response, followed by

oral therapy.

Metoprolol (Lopressor), 5 mg IV every 5 min for three doses

Atenolol (Tenormin) 5 mg IV q5min x 2 doses

Esmolol (Brevibloc), initial IV dose of 50 micrograms/kg/min

and adjust up to 200-300 micrograms/kg/min
80 U/kg IVP, followed by 15 U/kg/hr. Goal: aPTT 50-70 sec

Enoxaparin (Lovenox)
Glycoprotein
IIb/IIIa
inhibitors
Adenosine diphosphate
receptor-inhibitor
Cardiac catheterization

1 mg/kg IV, followed by 1 mg/kg subcutaneously bid

Eptifibatide (Integrilin) or tirofiban (Aggrastat) for patients with
high-risk features in whom an early invasive approach is planned
Consider clopidogrel (Plavix) therapy, 300 mg x 1, then 75 mg qd.

Consideration of early invasive approach in patients at intermediate

to high risk and those in whom conservative
Initial treatment of acute coronary syndromes
Continuous cardiac monitoring and IV access should be initiated. Morphine, oxygen,
nitroglycerin, and aspirin ("MONA") should be administered to patients with ischemic-type chest pain
unless contraindicated.
Morphine is indicated for continuing pain unresponsive to nitrates. Morphine reduces ventricular
preload and oxygen requirements by venodilation. Administer morphine sulfate 2-4 mg IV every 5-10
minutes prn for pain or anxiety. C.Oxygen should be administered to all patients with ischemic-type chest
discomfort and suspected ACS for at least 2 to 3 hours.
Intravenous nitroglycerin Nitroglycerin is an analgesic for ischemic-type chest discomfort.
Nitroglycerin is indicated for the initial management of pain and ischemia unless contraindicated by
hypotension (SBP <90 mm Hg) or RV infarction. Continued use of IV nitroglycerin beyond 48 hours is
only indicated for recurrent angina or pulmonary congestion.. Initially, give up to three doses of 0.4 mg
sublingual NTG every five minutes or nitroglycerine aerosol, 1 spray sublingually every 5 minutes.
An infusion of intravenous NTG may be started at 10-20 mcg/min, titrating upward by 5-10
mcg/min every 5-10 minutes (maximum, 3 mcg/kg/min). Titrate to decrease the mean arterial pressure by
10% in normotensive patients and by 30% in those with hypertension. Slow or stop the infusion if the
SBP drops below 100 mm Hg.
Aspirin. Aspirin should be given as soon as possible to all patients with suspected ACS unless the
patient is allergic to it. Aspirin therapy reduces mortality after MI by 25%. A dose of 325 mg of aspirin
should be chewed and swallowed on day 1 and continued PO daily thereafter at a dose of 80 to 325 mg.
Clopidogrel (Plavix) may be used in patients who are allergic to aspirin as an initial dose of 75 to
300 mg, followed by a daily dose of 75 mg.
Combination aspirin, 81 mg qd, and clopidogrel (Plavix), 75 mg qd, should be considered in
patients who continue to have recurrent ischemia despite optimal doses of nitrates and beta-blockers.
Risk stratification, initial therapy, and evaluation for reperfusion in the emergency
department.
Table 4.
Risk stratification with the first 12-lead ECG

Use the 12-lead ECG to triage patients into 1 of 3 groups:

1. ST-segment elevation
2. ST-segment depression or T-wave inversion
3. Nondiagnostic or normal ECG
1. Patients with ischemic-type chest pain and ST -segment elevation >1 mm in 2 contiguous leads
have acute myocardial infarction. Immediate reperfusion therapy with thrombolytics or angioplasty is
recommended.
2.Patients with ischemic-type pain but normal or nondiagnostic ECGs or ECGs consistent with
ischemia (ST-segment depression only) do not have ST-segment elevation MI. These patients should not
be given fibrinolytic therapy.

3.Patients with normal or nondiagnostic ECGs usually do not have AMI, and they should be
further evaluated with serial cardiac enzymes, stress testing and determination of left ventricular function.
Management of ST-segment elevation myocardial infarction.
1. Patients with ST-segment elevation have AMI should receive reperfusion therapy with
fibrinolytics or percutaneous coronary intervention.
Reperfusion therapy:
Fibrinolytics Patients who present with ischemic pain and ST-segment elevation (>1 mm in >2
contiguous leads) within 6 hours of onset of persistent pain should receive fibrinolytic therapy unless
contraindicated. Patients with a new bundle branch block (obscuring ST-segment analysis) and history
suggesting acute MI should also receive fibrinolytics or percutaneous coronary intervention.
Indications and contraindications for thrombolysis.
Indications
1. ST in greater than or equal to 2 contiguous leads; greater than or equal to 1mm in limb leads,
or greater than or equal to 2 mm in precordial leads,
or new or presumably new LBBB;
ST segment depression of greater than or equal to 2 mm in V1 V2 (true posterior infarction), and
2. Anginal chest pain greater than 30 minutes but less than 12 hours unrelieved with NTG SL
Absolute contraindications:
1. Previous hemorrhagic stroke at any time; other strokes or cerebrovascular events within one
year
2. Known intracranial neoplasm
3. Active internal bleeding (does not include menses)
4. Suspected aortic dissection
Relative contraindications:
1. Severe uncontrolled hypertension on presentation (greater than 180/110 mmHg)
2. History of prior cerebrovascular accident or known intracerebral pathology not covered in
above absolute contraindications
3. Current use of anticoagulants in therapeutic doses (INR greater than or equal to 2.0-3.0); known
bleeding diathesis
4. Recent trauma (including head trauma) within 2-4 weeks
5. Major surgery in past 3-6 months
6. Noncompressible vascular punctures
7. Recent internal bleeding
8. For streptokinase/anistreplase: prior exposure (especially within 5 days to 2 years) or prior
allergic reaction
9. Pregnancy
10. Active peptic ulcer
11. History of chronic hypertension
Table 5.
Treatment recommendations for ST-segment myocardial infarction.
Supportive care for chest pain:
All patients should receive supplemental oxygen, 2 L/min by nasal canula, for a minimum of
three hours;
Two large-bore IVs should be placed
Analgesic morphine sulfate

Peripheral venous and arterial dilation;

Blocks sympathetic efferent discharge at CNS level; reduces preload and afterload - good
with CHF
Side effects - hypotension and bradycardia occur rarely; respiratory depression with
severe COPD rare in setting of severe chest pain or pulmonary edema
Good dose response, easily reversible; 2- 5mg every 5-30 min (sometimes >30mg)
Aspirin:
Inclusion
Clinical symptoms or suspicion of AMI
Exclusion
Aspirin allergy, active GI bleeding
Recommendation Chew and swallow one dose of1 60-325 mg, then orally qd
Thrombolytics:
Inclusion
All patients with ischemic pain and ST-segment elevation (>1 mm in
>2 contiguous leads) within 6 hours of onset of persistent pain, age <75
years. All patients with a new bundle branch block and history suggesting
acute MI.
Exclusion
Active internal bleeding; history of cerebrovascular accident; recent
intracranial or intraspinal surgery or trauma; intracranial neoplasm,
arteriovenous malformation, or aneurysm; known bleeding diathesis; severe
uncontrolled hypertension.
Recommendation
Reteplase (Retavase) 10 U IVP over 2 min x 2. Give second dose of 10
U 30 min after first dose
OR Tenecteplase (TNKase): <60 kg: 30 mg IVP; 60-69 kg: 35 mg
IVP; 70-79 kg: 40 mg IVP; 80-89 kg: 45 mg IVP; >90 kg: 50 mg IVP
OR t-PA (Alteplase, Activase) 15 mg IV over 2 minutes, then 0.75
mg/kg (max 50 mg) IV over 30 min, followed by 0.5 mg/kg (max 35 mg) IV
over 30 min.
Heparin:
Inclusion
Administer concurrently with thrombolysis
Exclusion
Active internal or CNS bleeding
Recommendation Heparin 60 U/kg (max 4000 U) IVP, followed by 12 U/kg/hr (max 1000 U/h)
continuous IV infusion x 48 hours. Maintain aPTT 50-70 seconds
Beta-Blockade:
Inclusion
All patients with the diagnosis of AMI. Begin within 12 hours of diagnosis of
AMI
Exclusion
Severe COPD, hypotension, bradycardia, AV block, pulmonary edema,
cardiogenic shock
Recommendation Metoprolol (Lopressor), 5 mg IV push every 5 minutes for three doses;
followed by 25 mg PO bid. Titrate up to 100 mg PO bid OR Atenolol
(Tenormin), 5 mg IV, repeated in 5 minutes, followed by 50-100 mg PO qd.
Nitrates:
Inclusion
All patients with ischemic-type chest pain
Exclusion
Hypotension; caution in right ventricular infarction
Recommendation 0.4 mg NTG initially q 5 minutes, up to 3 doses or nitroglycerine aerosol, 1
spray sublingually every 5 minutes. IV infusion of NTG at 10-20 mcg/min,
titrating upward by 5-10 mcg/min q 5-10 minutes (max 3 mcg/kg/min). Slow
or stop infusion if systolic BP <90 mm Hg
ACE-Inhibitors or angiotensin receptor blockers:

Inclusion

All patients with the diagnosis of AMI. Initiate treatment within 24 hours
after AMI
Exclusion
Bilateral renal artery stenosis, angioedema caused by previous treatment
Recommendation Lisinopril (Prinivil) 2.5-5 mg qd, titrate to 1020 mg qd. Maintain systolic BP
>100 mmHg or Valsartan (Diovan) 40 mg bid, titrate to 160 mg bid
Percutaneous coronary intervention (PCI). PCI is preferable to thrombolytic therapy if
performed in a timely fashion by individuals skilled in the procedure. Coronary angioplasty provides
higher rates than thrombolytics and is associated with lower rates of reocclusion and postinfarction
ischemia and intracerebral bleed than fibrinolytic therapy.
Patients at high risk for mortality or severe LV dysfunction with signs of shock, pulmonary
congestion, heart rate >100 bpm, and SBP <100 mm Hg should be sent to facilities capable of performing
cardiac catheterization and rapid revascularization. When available within 90 minutes, PCI is
recommended for all patients, particularly those who have a high risk of bleeding with fibrinolytic
therapy.
Management of non-ST segment myocardial infarction and unstable angina
Anti-ischemic therapy
Once unstable angina or non-ST-segment elevation MI has been identified, standard anti-ischemic
treatments should be initiated.
Oxygen is indicated for patients with hypoxemia, cyanosis, or respiratory distress. Oxygen should
be administered for at least the initial acute phase in all patients and longer in patients with congestive
heart failure or a documented oxygen saturation of less than 92%.
Nitrates. Patients with ongoing chest pain should be given a 0.4-mg tablet of nitroglycerin
(NitroQuick, Nitrostat) sublingually every 5 minutes for a total of three tablets in 15 minutes. If angina
persists, continuous intravenous infusion of nitroglycerin starting at 10 micrograms/min should be
instituted. Adjustments to 100 to 150 micrograms/min may be made as needed for pain if blood pressure
permits. Tolerance to continuous nitroglycerin administration can develop after 24 hours.
Morphine. Intravenous morphine sulfate may be administered when ischemic chest pain is not
relieved with nitroglycerin or when acute pulmonary congestion or severe agitation is noted.
Beta-Blockers. Beta-blockade remains an important mainstay of therapy for unstable angina and
non-ST-segment elevation MI. It helps reduce cardiac workload and myocardial oxygen demand as well
as improve blood flow in coronary arteries. Unless contraindicated, beta-blockers should always be given
to patients presenting with an unstable coronary syndrome.
Intravenous therapy should be administered even when patients are already taking oral betablockers. Options include metoprolol (Lopressor), 5 mg given intravenously every 5 minutes for a total of
15 mg. Esmolol (Brevibloc) infusion starting at 50 micrograms/kg per minute for a maximum dose of 200
to 300 micrograms/kg per minute can also be used. The target heart rate with beta-blockade is less than 60
beats per minute.
Angiotensin-converting enzyme (ACE) inhibitors should be given early on in patients with left
ventricular dysfunction or evidence of congestive heart failure or diabetes mellitus. 7.Intra-aortic balloon
pump may be considered in patients with severe ischemia refractory to intensive medical therapy or in
hemodynamically unstable patients (eg, cardiogenic shock) before or after coronary angiography.
Anticoagulant therapy. .
Low-molecular-weight heparins. The low-molecular-weight heparins have a longer half-life than
unfractionated heparin and thus allow subcutaneous injections to be given twice daily. In addition, these

agents do not require serial monitoring or frequent dose adjustments. Heparin-induced thrombocytopenia
is less common with low-molecular-weight heparins than with unfractionated heparin.
Enoxaparin (Lovenox) use in patients with non-ST-segment elevation acute coronary syndromes
significantly reduces the risk of death, MI, recurrent angina, and need for urgent revascularization
compared to unfractionated heparin. Enoxaparin (Lovenox) should be considered as a replacement for
unfractionated heparin in non-ST-segment elevation acute coronary syndromes. Enoxaparin (Lovenox)
1.0 mg/kg SQ q12h.
Table 6.
Heparin and ST-segment depression and nonQ-wave MI/Unstable angina

IV heparin therapy for 3 to 5 days is standard for high-risk and some intermediate-risk
patients. Treat for 48 hours, then individualized therapy.
LMWH is preferred over IV unfractionated heparin. Enoxaparin (Lovenox) 1.0 mg/kg SQ
q12h

Statin therapy. Use of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) as

part of an early, aggressive lipid-lowering approach results in improved endothelial function, vasodilation,
decreased platelet aggregation, and plaque stabilization.
Antiplatelet therapy Antiplatelet drug therapy is a crucial component of management of acute
coronary syndromes. The risk of death or nonfatal MI can be reduced with early antiplatelet therapy in
patients with unstable angina or non-ST-segment elevation MI.
Aspirin should be administered as soon as possible after presentation of an acute coronary
syndrome and continued indefinitely. Patients not previously given aspirin should chew the initial dose to
rapidly achieve high blood levels. Aspirin therapy should be continued at a daily dose of 325 mg.
Clopidogrel (Plavix) is a thienopyridine derivative that exerts an antiplatelet effect by blocking
adenosine diphosphate-dependent platelet activation. Clopidogrel should be added to aspirin therapy as
part of the antiplatelet regimen in acute coronary syndromes at a daily dose of 75 mg for nine to 12
months.
Glycoprotein IIb-IIIa receptor antagonists The GpIIb-IIIa receptor on the platelet surface serves as
the final common pathway for platelet-platelet interaction and thrombus formation.
Three GpIIb-IIIa inhibitor drugs are commercially available: abciximab (ReoPro), eptifibatide
(Integrilin), and tirofiban (Aggrastat). The various GpIIb-IIIa receptor antagonists have been approved for
treatment of medically refractory unstable angina. However, abciximab is not currently approved without
planned percutaneous coronary intervention or cardiac catheterization.
Bleeding remains the most frequent complication of GpIIb-IIIa inhibitors. Severe
thrombocytopenia (platelets, <50 X 103/microliters) occurs in 0.1% to 0.7% of cases. Contraindications
include cerebrovascular accident or neurosurgical intervention within less than 6 months, surgery or
gastrointestinal hemorrhage within less than 6 weeks, intracranial malignancy, and platelet count less than
100 X 103/microliters. Eptifibatide and tirofiban require dose adjustments with a serum creatinine level of
more than 2 mg/dL.
Because of the significant risk of bleeding with use of GpIIb-IIIa antagonists (which are given in
conjunction with other antiplatelet and anticoagulation treatment), routine surveillance for mucocutaneous
bleeding, bleeding at the vascular access site, and spontaneous bleeding is important. Hemoglobin level
and platelet counts should be measured daily.

GpIIb-IIIa antagonist therapy should be strongly considered for patients who have high-risk
features, such as elevated levels of cardiac markers, dynamic ST-segment changes, and refractory chest
pain and in whom early angiography and percutaneous coronary intervention are planned.
Intravenous GP blocker dosages Abciximab (ReoPro), 0.25 mg/kg IVP over 2 min, then 0.125
mcg/kg/min (max 10 mcg/min) for 12 hours.
Eptifibatide (Integrilin), 180 mcg/kg IVP over 2 min, then 2 mcg/kg/min for 24-72 hours. Use 1.0
mcg/kg/min if creatinine is >2.0 mg/dL, or creatinine clearance < 50 mL/min.
Tirofiban (Aggrastat), 0.4 mcg/kg/min for 30 min, then 0.1 mcg/kg/min IV infusion for 24-72
hours. Reduce dosage by 50% if the creatine clearance is <30 mL/min.
Conservative versus early invasive approach.
Early invasive approach. An early invasive approach was most beneficial in patients with
intermediate-or high-risk factors. Such factors include an elevated troponin level, ST-segment changes or
T-wave inversion, age greater than 75 years, diabetes, and an elevated TIMI risk score (table 8). In lowrisk patients, a routine early invasive approach is not recommended, unless the patient continues to have
recurrent chest pain despite anti-ischemic therapy with nitrates and beta-blockers.
Table 7.
Non-ST-segment elevation acute coronary syndrome patients at high risk of death or
myocardial infarction
At least one of the following features must be present
Prolonged ongoing rest pain >20 minutes
Elevated cardiac troponin (TnT or TnI >0.1 ng/mL)
New ST-segment depression
Sustained ventricular tachycardia
Pulmonary edema, most likely due to ischemia
New or worsening mitral regurgitation murmur
S3 or new/worsening rales
Hypotension, bradycardia, tachycardia
Age >75 years
TIMI Risk Score: A simple, effective tool for initial risk assessment. Patients with ACS who
are diagnosed as having UA/NSTEMI, present with varying degrees of ischemic risk. A multivariate
analysis that adjusts for several prognostic variables simultaneously provides a more accurate tool for risk
stratification. In addition, the prognostic scoring system must be readily applicable using standard patient
features that are part of the routine, initial medical evaluation. The TIMI risk score, developed to address
this need, has been shown to predict the risk of ischemic events
Table 8.
TIMI risk score for STEMI
HISTORICAL
Age 75
65-74
DM or HTN or angina
EXAM
SBP < 100 mmHg
HR >100 bpm
Killip II-IV
Weight < 67 kg (150 lb)

POINTS
3
2
1
3
2
2
1

PRESENTATION
Anterior STE or LBBB
Time to Rx > 4 hrs
RISK SCORE = Total points (0 -14)

1
1

Because of the complex profiles of these patients, clinicians individually assess prognosis to
formulate plans for treatment. The TIMI risk score may be used as a basis for therapeutic decisionmaking. Prognostication of patient risk allows clinicians to triage patients to the optimum location for
medical care, such as the ICU vs hospital ward vs outpatient care. The TIMI risk score also helps identify
patients for whom antithrombotic therapies would be especially effective, even those in whom the
treatment benefit may be smaller. As demonstrated in the charts below, the TIMI risk score demonstrates
that the higher the score, the greater the risk of death or ischemic events. Therefore, patients with higher
risk scores may be candidates for early, aggressive treatment.
An early invasive approach is most beneficial for patients presenting with elevated levels of
cardiac markers, significant ST-segment depression, recurrent angina at a low level of activity despite
medical therapy, recurrent angina and symptoms of heart failure, marked abnormalities on noninvasive
stress testing, sustained ventricular tachycardia, recent percutaneous coronary intervention, or prior
CABG.
Patients who are not appropriate candidates for revascularization because of significant or
extensive comorbidities should undergo conservative management.
Management of patients with a nondiagnostic ECG/ Patients with a nondiagnostic ECG who
have an indeterminate or a low risk of MI should receive aspirin while undergoing serial cardiac enzyme
studies and repeat ECGs. Treadmill stress testing and echocardiography is recommended for patients with
a suspicion of coronary ischemia.
Question:
1. Define acute coronary syndrome (ACS).
2. Describe the differing criteria for unstable angina (UA), non-ST-segment elevated myocardial
infarction (NSTEMI), and ST-segment myocardial infarction (STEMI)
3. Compare and contrast the various types of angina.
4. Discuss the underlying pathophysiology of coronary artery disease and acute coronary
syndrome.
5. Explain the various complications that can result from ACS when treatment is not implemented
or not effective.
6. Perform a thorough assessment of chest pain by using focused questions.
7. Describe the data regarding chest pain description and the patients history and physical
examination to assist in ruling out alternative causes for chest pain.
8. Identify unique anginal characteristics of the elderly.
9. Identify abnormal ECG patterns indicative of CAD (Coronary Artery Disease) for a patient who
is experiencing angina.
10. Compare and contrast the lab tests used in evaluating suspected ACS.
11. Differentiate between the noninvasive diagnostic tests (echocardiogram and stress tests) that
are used to evaluate suspected ACS.
12. Compare and contrast the pharmacologic therapies that are commonly used for patients with
ACS including antiplatelet agents, heparin, nitrates, beta-blockers and calcium-channel blockers.

COMPLICATIONS OF ACUTE MI
A variety of complications can occur after myocardial infarction even when treatment is initiated
promptly.
Complications of the acute period of the myocardial infarction:

Arrhythmia and conduction disturbances

Acute left ventricular failure (cardiac asthma, pulmonary oedema)

Cardiogenic shock

Acute aneurysm of heart

Ventricular septal rupture (VSR)

Papillary muscle rupture or dysfunction (causing mitral regurgitation)

Cardiac free wall rupture

Pericarditis

Tromboembolic episodes

Acute erosions and ulcers of the gastrointestinal tract

Complications of the subacute period of the myocardial infarction:

Arrhythmia and conduction disturbances

Chronic heart failure

Chronic aneurysm of the heart

Tromboembolic episodes

Postmyocardial infarction syndrome (Dressler's syndrome )

ostmyocardial infarction stenocardia

Ventricular tachyarrhythmia post Ml

1
Accelerated idioventricular rhythm
Common (up to 20%) in patients with early reperfusion in first 48 hours.
Usually self limiting and short lasting with no haemodynamic effects
If symptomatic, accelerating sinus rate with atrial pacing or atropine may be of value. Suppressive
anti-arrhythmic therapy (lignocaine, amiodarone) is only recommended with degeneration into malignant
ventricular tachyarrhythmias.
2
Ventricular premature beats (VPB)
Common and not related to incidence of sustained VT/VF
Generally treated conservatively. Aim to correct acid-base and electrolyte abnormalities (aim K +
>4.0mmol/L and Mg2+>1.0mmol/L)
Peri-infarction -blockade reduces VPB.
3
Non-sustained and monomorphic ventricular tachycardia (VT)
Associated with a worse clinical outcome
Correct reversible features such as electrolyte abnormalities and acid-base balance
DC cardioversion for haemodynamic instability
Non-sustained VT and haemodynamically stable VT (slow HR <100bpm) can be treated with
amiodarone (300mg bolus iv over 30 minutes, followed by 1.2g infusion over 24 hours). Lignocaine is no
longer recommended as fist line. Procainamide is an effective alternative, but is arrhythmogenic
For incessant VT on amiodarone consider overdrive pacing.
4
Ventricular fibrillation and polymorphic VT
A medical emergency and requires immediate defibrillation

 In refractory VF consider vasopressin 40U iv bolus

Amiodarone 300mg iv bolus to be continued as an infusion (see above) if output restored
Atrial tachyarrhythmia post Ml

Includes supraventricular tachycardia (SVT), atrial fibrillation (AF), and atrial flutter.

If patient is haemodynamically unstable must undergo immediate synchronized DC

cardioversion

Haemodynamically stable patients can be treated with digoxin, -blockers, and/or calcium
channel blockers

Amiodarone can be used to restore sinus rhythm. However, it is very effective in controlling
rate. Class I agents should generally be avoided as they increase mortality.
In AF and flutter patients should undergo anti-coagulation to reduce embolic complications if there
are no contraindications
Brad/arrhythmias and indications for pacing
Alternating or isolated RBBB/LBBB do not need pacing (unless haemodynamically unstable or
progression to higher levels of block). New bifasicular block (RBBB with either LAD or RAD) or BBB
with first-degree AV block may require prophylactic pacing depending on the clinical picture Indications
for pacing should not delay reperfusion therapy. Venous access (femoral or internal jugular vein) should be
obtained first and pacing wire inserted later. External temporary cardiac pacing, atropine (300pg to 3mg iv
bolus), and isoprenaline can be used to buy time.
Bradyarrhythmias post Ml
1
First-degree AV block
Common and no treatment required
Significant PR prolongation (>0.20s) is a contraindication to -blockade.
2
Second-degree AV block
This indicates a large infarction affecting conducting systems and mortality is generally increased in this
group of patients
Mobitz type I is self-limiting with no symptoms. Generally, requires no specific treatment. If
symptomatic or progression to complete heart block will need temporary pacing
Mobitz type II, 2:1, 3:1 should be treated with temporary pacing regardless of whether it
progresses to complete heart block.
3
Third-degree AV block
In the context of an inferior Ml can be transient and does not require temporary pacing unless there
is haemodynamic instability or an escape rhythm of <40bpm
Temporary pacing is required with anterior Ml and unstable inferior Ml.
Hypotension and shock post Ml
The important principles in managing hypotensive patients with myocardial infarction are:

If the patient is well perfused peripherally, no pharmacological ntervention is required.

Consider lying the patient flat with legs elevated if necessary, provided there is no pulmonary edema

Try to correct any arrhythmia, hypoxia, or acidosis

Arrange for an urgent Echo to exclude a mechanical cause for hypotension (e.g. mitral
regurgitation, VSD, ventricular aneurysm) that may require urgent surgery.
Patients may be divided into two sub-groups - hypotension with pulmonary edema and hypotension
without pulmonary edema.
Left Ventricular Dysfunction and Failure

Function of the ventricle is affected within seconds of occlusion of blood flow, and adverse
remodeling can occur within the early course of an acute myocardial infarction (AMI) and
continues over following months and years.
Results typically when the left coronary system is the culprit for ischemia
Killip Classification
I no evidence of pulmonary congestion or shock
II mild pulmonary congestion or an isolated S3
III pulmonary edema
IV hypotension and evidence of shock
Management
Revascularization is ischemia is the primary cause of failure
Involves the use of diurectics to clear pulmonary congestion
Can involve the use of inotropic support to support systolic pressure with the goal of
maintaining end-organ perfusion, and/or improve diuresis
Can involve the use of ACEI, if systolic blood pressure will tolerate, to afterload reduce
the heart, especially with mitral insufficiency
Can involve the use of intra-aortic balloon pump therapy to support cardiac functioning,
through increased coronary perfusion, and afterload reduction
The use of digoxin may have some added benefit by increasing inotropicity of the
myocardium with lower filling pressures
CARDIOGENIC SHOCK
Cardiogenic shock is characterized by a decreased pumping ability of the heart that causes a shock
like state with inadequate perfusion to the tissues. Shock, in turn, is the most common cause of death in
hospitalized patients with acute myocardial infarction; reported mortality rates range from 50% to 80%.
Rapid evaluation and prompt initiation of supportive measures and definitive therapy in patients with
cardiogenic shock may improve early and long-term outcomes.
Definition
The clinical definition of cardiogenic shock is decreased cardiac output and evidence of tissue
hypoxia in the presence of adequate intravascular volume. Hemodynamic criteria are sustained
hypotension (systolic blood pressure less than 90 mm Hg for at least 30 minutes) and a reduced cardiac
index less than 2.2 L/min per m2 in the presence of elevated pulmonary capillary occlusion pressure
greater than <15 mm Hg.
Circulatory shock is diagnosed at the bedside by observing hypotension and clinical signs
indicating poor tissue perfusion, including oliguria; clouded sensorium; and cool, mottled extremities.
Cardiogenic shock is diagnosed after documentation of myocardial dysfunction and exclusion or
correction of such factors as hypovolemia, hypoxia, and acidosis.
Incidence
Recent estimates of the incidence of cardiogenic shock have ranged from 5% to 10% of patients
with myocardial infarction. The precise incidence is difficult to measure because patients who die before
reaching the hospital are not given the diagnosis. In contrast, early and aggressive monitoring can
increase the apparent incidence of cardiogenic shock.

Cause and Epidemiology

The most common cause of cardiogenic shock is extensive acute myocardial infarction, although a
smaller infarction in a patient with previously compromised left ventricular function may also precipitate
shock.
Shock that has a delayed onset may result from infarction extension, reocclusion of a previously
patent infracted artery, or decompensation of myocardial function in the noninfarction zone because of
metabolic abnormalities. It is important to recognize that large areas of nonfunctional but viable
myocardium can also cause or contribute to the development of cardiogenic shock in patients after
myocardial infarction.
Cardiogenic shock can also be caused by mechanical complications - such as acute mitral
regurgitation, rupture of the interventricular septum, or rupture of the free wall - or by large right
ventricular infarctions. Other causes of cardiogenic shock include myocarditis, end-stage cardiomyopathy,
myocardial contusion, septic shock with severe myocardial depression, myocardial dysfunction after
prolonged cardiopulmonary bypass, valvular heart disease, and hypertrophic obstructive cardiomyopathy
(Table 1).
Table 1.
Causes of Cardiogenic Shock
Acute myocardial infarction and complications of acute MI
- Pump failure
- Large infarction
- Smaller infarction with preexisting left ventricular dysfunction
- Infarction extension
- Reinfarction
- Infarction expansion
- Mechanical complications
- Acute mitral regurgitation caused by papillary muscle rupture
- Ventricular septal defect
- Free-wall rupture
- Pericardial tamponade
- Right ventricular infarction
- Left ventricular aneurism
Other conditions
- End-stage cardiomyopathy
- Myocarditis
- Myocardial contusion
- Prolonged cardiopulmonary bypass
- Septic shock with severe myocardial depression
- Left ventricular outflow tract obstruction
- Aortic stenosis
- Hypertrophic obstructive cardiomyopathy
- Obstruction to left ventricular filling
- Mitral stenosis
- Left atrial myxoma
- Acute mitral regurgitation (chordal rupture)

- Acute aortic insufficiency

Patients may have cardiogenic shock at initial presentation, but shock often evolves over several
hours after AMI. Patients may have cardiogenic shock at initial presentation, but shock often evolves over
several hours. In the 75% of patients developed cardiogenic shock within 24 hours after presentation; the
median delay was 7 hours from onset of infarction. Results from the among patients with myocardial
infarction, shock more likely to develop in those who are elderly, are diabetic, and have anterior infarction
and dysrhythmia.
As compared with patients who have acute myocardial infarction without cardiogenic shock,
patients who have shock are older, more frequently have anterior myocardial infarction, more often have
had a previous infarction, and more commonly have a history of angina or congestive heart failure.
Several studies have found a higher prevalence of diabetes among patients with cardiogenic shock,
but other risk factors for the development of atherosclerosis are not more common among patients in
whom shock develops.
Pathological and angiographic studies have consistently found a greater prevalence of occlusion of
the left anterior descending artery, multivessel coronary artery disease, and persistent occlusion of the
infarct-related artery among patients with cardiogenic shock. Patients in whom cardiogenic shock
develops after hospital admission tend to be older than others, are more apt to have a history of infarction
and diabetes mellitus, and have depressed systolic function with higher creatine kinase or lactate
dehydrogenase values.
The results of recent angiographic and echocardiographic studies emphasize the importance of the
zone of myocardium remote from the acute infarction in the development of cardiogenic shock. The
normal response of one wall of the heart to infarction is to develop "compensatory" hyperkinesis of the
uninvolved myocardium. When the uninvolved myocardium is fibrotic or when its blood flow is
compromised by high-grade stenosis, this compensatory mechanism is thwarted. The absence of
hyperkinesis in the ventricular wall opposite the region of the acute infarct is an important risk factor for
the development of cardiogenic shock and for death.
Pathophysiology of Cardiogenic Shock
Cellular Pathology. Tissue hypoperfusion and consequent cellular hypoxia lead to anaerobic
glycolysis, with depletion of adenosine triphosphate and intracellular energy reserves. Anaerobic
glycolysis also causes accumulation of lactic acid and resultant intracellular acidosis. Failure of energydependent ion transport pumps decreases transmembrane potential, causing intracellular accumulation of
sodium and calcium and myocyte swelling. Cellular ischemia and intracellular calcium accumulation can
activate intracellular proteases. If the ischemia is severe and prolonged, myocardial cellular injury can
become irreversible, with the classic pattern of myonecrosis: mitochondrial swelling; accumulation of
denatured proteins and chromatin in the cytoplasm; lysosomal breakdown; and fracture of the
mitochondria, nuclear envelope, and plasma membrane.
Neurohormonal regulation. Initial compensatory mechanisms include activation of the
sympathetic nervous system, effects on renal and neurohormonal regulation, and local vasoregulation
(Figure 1).
The activation of the sympathetic nervous system is triggered by baroreceptors and
chemoreceptors, leading to an increase in heart rate and arterial and venous vasoconstriction, an increase
in myocardial contractility, and shifting of fluid into the vascular compartment.
The renin-angiotensin system is activated by inadequate renal perfusion pressure and sympathetic
stimulation of the renal nerves. An excess of angiotensin II leads to peripheral vasoconstriction and

aldosterone synthesis, which in turn increases sodium and water resorption by the kidneys, thus raising
blood volume. Distention of the atria leads to the production of atrial natriuretic peptide, which enhances
the renal excretion of salt and water while reducing renin formation and counteracting the effects of
angiotensin II.

Figure 1. The Vicious Circle of Neurohormonal and Mechanical Events That Lead to Death
in Patients with Cardiogenic Shock.
A reduction in cardiac output triggers a spiraling series of events that produce further compromise,
leading to death, unless successfully countered by homeostatic mechanisms or external therapeutic forces.
A combination of therapeutic approaches counteracting different components of the spiral is usually
required to reverse the syndrome. ANP denotes atrial natriuretic peptide. The plus and minus signs
indicate enhancement (+) or blockage (-) of the processes to which the arrows point. Arrows pointing up
indicate an increase, and arrows pointing down a decrease.
Finally, production of antidiuretic hormone is increased by hypotension, which also causes an
increase in renal water resorption. Hypoperfusion results in the release of endogenous substances
including myocardial depressant factor, histamine, bradykinin, thromboxane, cytokines, leukotrienes,
platelet-activating factor, and lactic acids.
These substances further inhibit cardiac function, thereby increasing myocardial depression and
worsening the shock state; this, in turn, increases the release of these substances. An extensive body of
literature supports the existence of endogenously produced myocardial depressant factor. Myocardial

depressant factor is a low-molecular-weight protein that is believed to be released from pancreatic

lysosomes during shocklike states. Myocardial depressant factor causes direct myocardial depression by
an unknown mechanism.
Local effects on tissues initially include the accumulation of vasoactive metabolites causing
arteriolar and capillary vasodilatation. Autoregulation leads to the redistribution of blood away from the
skin, intestines, and skeletal muscle in favor of the brain, heart, and kidneys. Eventually, decreased
perfusion pressure, especially in the presence of multivessel obstructive coronary disease, leads to further
depression of myocardial contractility, and the compensatory peripheral mechanisms are overwhelmed by
the progressive deterioration of cardiac function.
Systemic Effects. Similar events occur on a more macro level as well. Cardiac dysfunction in
patients with cardiogenic shock is usually initiated by myocardial infarction or ischemia. The myocardial
dysfunction resulting from ischemia worsens that ischemia, creating a down-ward spiral (Figure 2). When
a critical mass of left ventricular myocardium is ischemic or necrotic and fails to pump, stroke volume
and cardiac output decrease. Myocardial perfusion, which depends on the pressure gradient between the
coronary arterial system and the left ventricle and on the duration of diastole, is compromised by
hypotension and tachycardia.

Figure 2. The downward spiral in cardiogenic shock.

LVEDP = left ventricular end-diastolic pressure.
This, in turn, exacerbates ischemia. The increased ventricular diastolic pressures caused by pump
failure further reduce coronary perfusion pressure, and the additional wall stress elevates myocardial
oxygen requirements, further worsening ischemia. Decreased cardiac output also compromises systemic
perfusion, which can lead to lactic acidosis and further compromise of systolic performance.
When myocardial function is depressed, several compensatory mechanisms are activated,
including sympathetic stimulation to increase heart rate and contractility and renal fluid retention to
increase preload. These compensatory mechanisms may become maladaptive and can actually worsen the

situation when cardiogenic shock develops. Increased heart rate and contractility increase myocardial
oxygen demand and exacerbate ischemia. Fluid retention and impaired diastolic filling caused by
tachycardia and ischemia may result in pulmonary congestion and hypoxia.
Vasoconstriction to maintain blood pressure increases myocardial afterload, further impairing
cardiac performance and increasing myocardial oxygen demand. This increased demand, in the face of
inadequate perfusion, worsens ischemia and begins a vicious cycle that will end in death if uninterrupted
(Figure 2).
One important consequence of this downward spiral, in which ischemia worsens myocardial
performance, is that early intervention to relieve ischemia reduces the incidence of cardiogenic shock.
Reversible Myocardial Dysfunction. A key to understanding the pathophysiology and treatment of
cardiogenic shock is to realize that large areas of nonfunctional but viable myocardium can also cause or
contribute to the development of cardiogenic shock in patients after myocardial infarction (Figure 3).
This reversible dysfunction can be described in two main categories: stunning and hibernation.

Figure 3. Potential consequences of myocardial ischemia.

Myocardial stunning represents postischemic dysfunction that persists despite restoration of
normal blood flow; eventually, however, myocar dial performance recovers completely. The pathogenesis
of stunning has not been conclusively established but seems to involve a combination of oxidative stress,
perturbation of calcium homeostasis, and decreased myofilament responsiveness to calcium, all in the
setting of antecedent ischemia.
Hibernating myocardium is in a state of persistently impaired function at rest because of severely
reduced coronary blood flow; inherent in the definition of hibernating myocardium is the notion that
function can be normalized by improving blood flow. Hibernation can be seen as an adaptive response to
reduce contractile function of hypoperfused myocardium and restore equilibrium between flow and
function, thereby minimizing the potential for ischemia or necrosis. Revascularization of hibernating
myocardium can lead to improved myocardial function, and improved function seems to improve
prognosis.
Notion that some myocardial tissue may recover function emphasizes the importance of measures
to support hemodynamic and minimize myocardial necrosis in patients with shock.
Clinical Assessment

Most patients with cardiogenic shock have an AMI and, therefore, present with the constellation of
symptoms of acute cardiac ischemia (eg, chest pain, shortness of breath, diaphoresis, nausea and
vomiting). Patients experiencing cardiogenic shock also may present with pulmonary edema and
presyncopal or syncopal symptoms.
Patients with shock are usually ashen or cyanotic and can have cool skin and mottled extremities.
Cerebral hypoperfusion may cloud the sensorium. Pulses are rapid and faint and may be irregular if
arrhythmia is present. Jugular venous distention and pulmonary rales are usually present.
Physical. Physical examination often reveals that the patient is in the middle of an AMI. Clinical
assessment begins with attention to the vital signs.
Although the patient may eventually require endotracheal intubation, the airway usually is patent
initially. Breathing may be labored, with audible coarse crackles or wheezing. As in any shock like state,
circulation is markedly impaired.
Patients present with poor peripheral pulses, and varying degrees of end-organ dysfunction (eg,
decreased mental function and urinary output). Initial vital sign assessment should include BP
measurements in both arms to evaluate possible thoracic aortic aneurysm or dissection. Vital signs should
be regularly updated with continuous noninvasive physiologic monitoring.
Neck examination may reveal jugular venous distention, which may be prominent. This finding is
evidence of right ventricular failure. With increasing ventricular dysfunction, florid pulmonary edema and
severe hypotension may develop. Auscultation of the chest may reveal varying degrees of congestive
heart failure.
Careful cardiac examination may reveal mechanical causes of cardiogenic shock that are readily
amenable to surgical intervention; without needed surgery, the mortality rate is dismal. Causes amenable
to surgery include papillary rupture, valvular dysfunction, myocardial wall or septal rupture, cardiac
tamponade, and aortic aneurysm.
Loud murmurs may indicate a valvular dysfunction, whereas muffled heart tones with jugular
venous distention and pulsus paradoxus may suggest tamponade.
Cardiogenic shock is an emergency. The clinician must initiate therapy before shock irreversibly
damages vital organs; at the same time, he or she must perform the clinical assessment required to
understand the cause of shock and target therapy to that cause.
A practical approach is to make a rapid initial evaluation on the basis of a limited history, physical
examination, and specific diagnostic procedures (Figure 4).
Lab Studies. No one test is completely sensitive or specific for cardiogenic shock. Laboratory
studies are directed at the potential underlying cause.
In most cases, the usual workup includes tests of all of the following, which usually are assessed
in cases of suspected cardiac ischemia:
Cardiac enzymes (eg, creatine kinase, troponin, myoglobin)
CBC
Electrolytes
Coagulation profile (eg, prothrombin time, activated partial thromboplastin time)
An ABG test may be useful to evaluate acid-base balance, because acidosis can have a
particularly deleterious effect on myocardial function.
Imaging Studies. A portable chest radiograph is helpful because it gives an overall impression of
the cardiac size, pulmonary vascularity, and coexistent pulmonary pathology, and it provides a rough
estimate of mediastinal and aortic sizes in the event that an aortic etiology is being considered.

Other Tests. Electrocardiography should be performed immediately. An ECG is helpful if it

reveals an acute injury pattern consistent with an AMI. A normal ECG, however, does not rule out the
possibility of AMI. ECGs are often most helpful when they can be compared with previous tracings.
An echocardiogram obtained in the cardiogenic shock can be extremely useful and should be
routine. Echocardiography provides information on overall and regional systolic function and can lead to
a rapid diagnosis of mechanical causes of shock, such as papillary muscle rupture and acute mitral
regurgitation, acute ventricular septal defect, and free-wall rupture and tamponade. Unsuspected severe
mitral regurgitation is not uncommon. In some cases, echocardiography may show findings that are
compatible with right ventricular infarction.
Invasive Procedures. Invasive hemodynamic monitoring can be useful to exclude volume
depletion, right ventricular infarction, and mechanical complications. The hemodynamic profile of
cardiogenic shock includes a pulmonary capillary occlusion pressure greater than 15 mm Hg and a
cardiac index less than 2.2 L/min per m2. It should be recognized that optimal filling pressures may be
greater than 15 mm Hg in individual patients because of left ventricular diastolic dysfunction.
Right-heart catheterization may show a step-up in oxygen saturation that is diagnostic of
ventricular septal rupture or a large V wave that suggests severe mitral regurgitation. The hemodynamic
profile of right ventricular infarction includes high right-side filling pressures in the presence of normal or
low occlusion pressures.

Figure 4. An approach to the diagnosis and treatment of cardiogenic shock caused by

myocardial infarction
CABG =coronary artery bypass grafting; IABP = intra-aortic balloon pumping.

Treatment.
Initial Management. The initial approach to the patient in cardiogenic shock should include:
fluid resuscitation unless pulmonary edema is present
central venous and arterial access,
bladder catheterization
and pulse oximetry
oxygenation and airway protection are critical; i
intubation and mechanical ventilation are often required, if only to reduce the work of breathing and
facilitate sedation and stabilization before cardiac catheterization.

Electrolyte abnormalities should be corrected. Hypokalemia and hypomagnesemia are

predisposing factors to ventricular arrhythmia, and acidosis can decrease contractile function.
Relief of pain and anxiety with morphine sulfate (or fentanyl if systolic pressure is compromised)
can reduce excessive sympathetic activity and decrease oxygen demand, preload, and afterload.
Arrhythmia and heart block may substantially affect cardiac output and should be corrected
promptly with antiarrhythmic drugs, cardioversion, or pacing.
Cardiology consultation has been shown to be associated with improved outcomes in patients with
myocardial infarction and is strongly indicated in the setting of cardiogenic shock. In addition,
medications proven to improve outcome after myocardial infarction, such as nitrates, b-blockers, and
angiotensin-converting enzyme inhibitors, may exacerbate hypotension in a patient with cardiogenic
shock; therefore, therapy with these medications should be discontinued until the patient stabilizes.
In patients with inadequate tissue perfusion and adequate intravascular volume, cardiovascular
support with inotropic agents should be initiated. Dobutamine, a selective 1-adrenergic receptor agonist,
can improve myocardial contractility and increase cardiac output without markedly changing heart rate or
systemic vascular resistance; it is the initial agent of choice in patients with systolic pressures greater than
80 mm Hg. Dobutamine may exacerbate hypotension in some patients and can precipitate
tachyarrhythmia. Dopamine acts directly on myocardial 1-adrenergic receptors and acts indirectly by
releasing norepinephrine. It has both inotropic and vasopressor effects, and its use is preferable in the
presence of systolic pressures less than 80 mm Hg. Tachycardia and increased peripheral resistance with
dopamine administration may exacerbate myocardial ischemia. In some situations, a combination of
dopamine and dobutamine can be more effective than either agent alone.
When hypotension remains refractory, norepinephrine - a natural catecholamine with potent and
1-adrenergic effects- may be necessary to maintain organ perfusion pressure. Catecholamine infusions
must be carefully titrated in patients with cardiogenic shock to maximize coronary perfusion pressure
with the least possible increase in myocardial oxygen demand.
Invasive hemodynamic monitoring can be extremely useful in allowing optimization of therapy in
these unstable patients because clinical estimates of filling pressure can be unreliable; in addition,
changes in myocardial performance, compliance, and therapeutic interventions can change cardiac output
and filling pressures precipitously.
PULMONARY EDEMA
Acute pulmonary edema is a generalized descriptive term for the accumulation of fluid within the
interstitial and/or the alveolar spaces of the lungs. This accumulation of fluid has a cause that may be
termed cardiogenic or non-cardiogenic.
Pulmonary edema of cardiogenic origin is usually due to failure of the left side of the heart.
Non-cardiogenic pulmonary edema is a clinical syndrome characterized by simultaneous presence
of severe hypoxemia, bilateral alveolar infiltrates on chest radiograph and no evidence of left atrial
hypertension/congestive heart failure.
Table 2.
Special forms of non-cardiogenic pulmonary edema.
Pharmaceutical
Narcotic overdose
Chemotherapy

Salicylate intoxication
Calcium antagonist overdose
Hydrochlorothiazide
Contrast fluids
High-altitutde
Neurogenic
Pulmonary embolism
Eclampsia
Post cardioversion
Post anaesthesia
Post cardiopulmonary bypass
Four conditions contribute to development of pulmonary edema:
excessive pulmonary venous return caused by increased intravascular fluid (excessive left
ventricle (LV) preload);
increased peripheral vascular resistance from hypertension or hyperadrenergic states (increased
LV afterload);
impaired myocardial contractility from either systolic or diastolic dysfunction;
disorders of rhythm and rate.
Differential diagnosis
The differentiation between hydrostatic (cardiogenic) and increased permeability edema (NCPE),
can usually be made through assessment of the clinical context in which it occurs and by means of
clinical and laboratory data. This approach may be difficult as there is overlapping of pathogenetic
mechanisms in the two forms.
For example, the primary hemodynamic event of cardiogenic pulmonary edema, that is increase in
intravascular pressure, may disrupt the capillary and alveolar membranes producing a NCPE. The basic
differences between the two
forms of pulmonary edema are provided by history, clinical examination and laboratory tests.
In NCPE, there is neither history of acute cardiac event nor underlying cardiac disease. In
cardiogenic pulmonary edema, clinical examination reveals low flow state (cool periphery), S3 gallop,
cardiomegaly, jugular venous distention and wet crackles. NCPE is usually high flow state (warm
periphery), with bounding pulses, no gallop, no jugular venous distention and with dry crackles.
Concerning laboratory tests, in cardiogenic pulmonary edema, we may have ECG signs of
ischemia or infarction, raised cardiac enzymes and perihilar distribution of congestion in chest x-ray.
Pulmonary capillary wedge pressure exceeds 18mmHg and the ratio of pulmonary edema fluid protein to
plasma protein concentration is less than 0.5.
On the contrary in NCPE, ECG and cardiac enzymes are usually normal, on chest x-ray there is
peripheral distribution of edema, pulmonary capillary wedge pressure is less than 18mmHg and the ratio
of pulmonary edema fluid protein to plasma protein concentration is 0.7 or above. Chest x-ray findings
usually appear late, at least 12 hours after the onset of cardiopulmonary symptoms.
It is stated that the value of chest radiography is limited in the differentiation of the two types of
pulmonary edema in severe cases. However, recent studies have suggested that chest radiography can be
used to distinguish these types of pulmonary edema, if careful attention is given to certain radiographic
features. In some studies, independent investigators (thoracic radiologists), managed to distinguish
NCPE from cardiogenic with an accuracy of 91%.

The distinguishing radiographic criteria of the two types of pulmonary edema are listed below:
1. In NCPE, the initial site of fluid accumulation is the pulmonary interstitium including
peribronchial cuffs and septal lines. This type of edema appears predominantly as alveolar filling, since
the altered (disrupted) alveolar-capillary membrane allows for the direct accumulation in the air spaces of
fluid that is too proteinaceous to be cleared via the interstitium.
In contrast, in cardiogenic pulmonary edema filling of air spaces (alveolar flooding) occurs when
the interstitial space is finally overwhelmed.
2. Kerley lines are never seen in increased permeability edema whereas they are a common
finding in cardiogenic. The appearance of Kerley lines in NCPE, indicates the coexistence of cardiogenic
pulmonary edema.
3. Patchy or peripheral pattern of edema is relatively specific for NCPE. Air bronchograms are
frequently seen in patients with NCPE. In cardiogenic pulmonary edema the distribution of edema is
central and pleural effusion usually coexists.
5. In NCPE, cardiac size, vascular pedicle width and pulmonary blood volume are usually normal.
On the contrary, in cardiogenic pulmonary edema cardiac size is increased, vascular pedicle width is
enlarged and there is inverted distribution of blood flow.
At the time of initial injury and several hours thereafter, the patient may be free of respiratory
symptoms or signs. The earliest sign is an increase in respiratory frequency followed shortly by dyspnea.
Whatever the underlying cause of pulmonary edema, analysis of arterial blood to assess the type and
degree of gas exchange abnormality is necessary, followed by institution of appropriate inhalation
therapeutic measures.
Arterial blood gas measurement in the earlier period will disclose a depressed PO2 and decreased
PCO2. At this point, oxygen given by mask or nasal prongs, results in a significant increase in the arterial
PO2.
Physical examination may be unremarkable, although a few fine inspiratory rales may be audible.
With progression, the patient becomes cyanotic and increasingly dyspneic and tachypneic. Rales are more
prominent and easily heard throughout both lung fields along with regions of tubular breath sounds.
At this stage, hypoxemia cannot be corrected by the simple administration of oxygen, and
mechanical ventilatory assistance must be initiated to provide adequate oxygenation of arterial blood.
Should this treatment be delayed, the combination of increasing tachypnea and smaller tidal
volume, results in a rising PCO2 and further fall in PO2 to fatal levels.
When there is hypoxemia (PO2 <60 mm Hg) without hypercapnia, enrichment of the inspired gas
may suffice and can be given either by nasal prongs or Venturi mask with reservoir, depending upon the
degree of oxygen enrichment required to elevate the PO2 sufficiently. If PO2 cannot be maintained at or
near 60 mmHg despite inhalation of 100% v2 at 20 liters per minute, or if there is progressive
hypercapnia, mechanical ventilation is necessary.
Mechanical ventilation
Mechanical ventilation is particularly useful in the treatment of patients with NCPE. If hypoxemia
is not corrected by mechanical ventilation or if toxic concentrations of oxygen are necessary for
prolonged periods, further improvements in arterial oxygenation at the same inspired oxygen
concentration or equivalent levels of arterial oxygenation at lower concentrations of oxygen can be
achieved by increasing end-expiratory lung volumes by the addition of positive end-expiratory pressure
(PEEP).
In these conditions we usually apply PEEP at 5-20 cm H2O. The role of PEEP is to avoid collapse
of alveoli and to maintain their inflation throughout the respiratory cycle.

As easy as 'LMNOP'
Remember the mnemonic LMNOP when treating a patient with acute pulmonary edema:
Lasix (furosemide) intravenous (IV), one to two times the patient's usual dose, or 40 mg if the
patient does not usually take the drug.
Morphine sulfate. Initial dose, 4 to 8 mg IV (subcutaneous administration is effective in milder
cases); may repeat in 2 to 4 hours. Avoid respiratory depression. Morphine increases venous capacity,
lowering left atrial pressure, and relieves anxiety, which reduces the efficiency of ventilation.
Nitroglycerin IV, 5 to 10 ug/min. Increase by 5 ug/min q 3 to 5 minutes. Reduces left ventricular
preload. Caution: may cause hypotension.
Oxygen, 100% given to obtain an arterial PO2>60 mm Hg.
Position patient sitting up with legs dangling over the side of the bed. This facilitates respiration
and reduces venous return.
Non-Cardiogenic Pulmonary Edema
"PONS"
P hosgene, paraquat, phenothiazines
O pioids, organophosphates
N itrogen dioxide
S alicylates
Modern management of PE is based on directly counteracting these physiologic abnormalities by
1) decreasing both preload and afterload (diuretics and vasodilators)
2) controlling excessive retention of salt and water (diuretics), and
3) improving cardiac contractility (inotropes).
More detail see figure 1.
Diuretics
Intravenous (iv) furosemide is traditionally administered to patients in order to relieve pulmonary
vascular congestion. Symptom relief was initially thought to be due to the rapid drug-induced diuresis
which reduces plasma volume and hence the pulmonary capillary pressure.
Although intravenously administered loop diuretics do have a rapid onset of action (5-10
minutes), emergency physicians have observed symptom relief in patients with APE much faster than
could have occurred from the diuretic effect alone.
Most experts recommend a dose of 1 mg/kg iv of furosemide to be given early although the
diuretic effect can be delayed by 20-30 minutes.
Vasodilators
Morphine
The use of morphine to treat APE evolved because of its vasodilatory and antianxiety effects.
Morphine causes venodilation through release of histamine; coinfusion of an histamine receptor blockade
completely abolished the venodilation whereas naloxone only had a marginal effect. The mechanism of
morphineinduced histamine release remains unknown though.
In addition, through reduced systemic catecholamines, morphine decreases heart rate, blood
pressure, cardiac contractility, and myocardial O2 consumption.1 The calming effect of morphine is
therefore advantageous in this setting, although it can lead to significant respiratory depression. For this
reason and because other drugs exist that give better results, morphine use in APE has declined over the
last few years.
Morphine is given in 2-5mg iv boluses, titrated to patients respiratory and neurologic status.
Nitrates

Nitrates react intracellularly to form nitric oxide which activates the enzyme guanylate cyclase,
leading to accumulation of cGMP. Cyclic GMP relaxes vascular smooth muscle by sequestering calcium
in the sarcoplasmic reticulum. Their effect is dose-dependent and varies on different vascular beds. At low
doses (50-80mcg/min), they cause mainly venodilation and a decrease in ventricular preload and wall
tension, thereby reducing myocardial O2 demand. With increasing doses (up to 200-300mcg/min),
nitrates cause afterload reduction by arteriodilation and a further decrease of ventricular wall tension and
O2 demand.
Many different routes of administration are available. They can be initiated most expeditiously via
the sublingual (s.l.) route even before iv access is established.
Sublingual tablets or transmucosal sprays have their onset of action within 2 minutes. The effect of
the tablets lasts approximately 20 minutes whereas the effect of the spray lasts 2 hours. Absorption from
topical nitro is erratic in diaphoretic, poorly perfused patients, making the cutaneous route less attractive
in this setting.
In 1998, the same Cotter compared the efficacy and safety of furosemide and ISDN in a
randomized trial of patients with severe APE and found that high dose ISDN (3 mg bolus iv every 5
minutes) plus 40mg of furosemide was more effective than high dose furosemide (80 mg every 15
minutes) plus low dose ISDN (1mg/hr, increased every 10 minutes by 1mg/hr), with need for mechanical
ventilation and frequency of myocardial infarction as the measured markers.
Drips are prepared by mixing 50mg of nitroglycerin in 250ml D5W (200mcg/ml) and usually
started at 3-6ml/hr (600-1200mcg/hr). As described above, boluses can also be given as long as patients
BP is adequately maintained.
Nitroprusside
Nitroprusside is a potent direct smooth muscle relaxing agent administered by continuous
infusion. Its rapid onset of action makes it ideal for titrating critical therapy. Continuous pressure
monitoring is mandatory in patients receiving this drug to avoid dangerous levels of hypotension that can
occur precipitously.
Nitroprusside is a balanced vasodilatating agent that results in both preload and afterload
reduction. It is the drug of choice in the therapy of patients in hypertensive crisis with APE. Patients
started on nitroprusside should be converted to oral balanced vasodilator therapy such as ACE inhibitors,
nitrates, and hydralazine as soon as they are clinically stable.
Drips are prepared by mixing 50mg nitroprusside in 250 ml D5W (200 mcg/ml) and usually
started at 0.25-10 mcg/kg/min.
Angiotensin-converting enzyme (ACE) inhibitors
Their mechanism of action is multifactorial. ACE inhibitors induce a relaxation of both arterial
resistance and venous capacitance which reduce both preload and afterload. They produce vasodilatation
without unfavorable effects on myocardial oxygenation (no increase in resting heart rate such as observed
with nitrates). They also relieve LV diastolic dysfunction by downregulating the renin-angiotensin
system and reducing adrenergic tone.
Like nitroglycerin, they can be given by multiple routes. Sublingually, onset of action is less than
10 minutes, a clinical decrease in dyspnea occurs in 15 minutes, and the peak effect is reached in 30
minutes. The oral tablet can be used for s.l. administration; placing a drop or two of water on the tablet
under the tongue helps it dissolve.
ACE inhibitor can also be given IV and because they work through an enzyme system, onset of
action is not significantly different than when given s.l.
Enalapril maleate is the only one available parenteral ACE inhibitor.

In view of its beneficial effects, enalapril should be given to all patients presenting with APE and
an adequate BP.
Dose: Enalapril 1.25 mg iv every 6 hours.
Captopril 25 mg s.l.
Inotropes
Although they can be used in severe pulmonary edema with hypotension, their main use is in PE
associated with shock. (see more ditaile cardiogenic shok)
Infarct extension and postinfarction ischemia.
Recurrent infarction in the region of infarction (infarct extension) in the first 10-14 days occurs in
approximately 10% of patients. It may be associated with prolonged or intermittent episodes of chest
pain. In many cases, the process is relatively silent, being detected on routine ECG, by laboratory testing,
or by onset or worsening of heart failure. Infarct extension is at least twice as common in non-Q wave
infarcts and is more likely to occur after successful thrombolytic therapy owing to residual jeopardized
myocardium. Diltiazem has been shown to reduce the rate of extension following non-Q wave infarction.
Approximately 30% of patients will have angina postinfarction. This is more common in patients
with angina prior to infarction and in non-Q wave infarction. Postinfarction angina is associated with
increased short- and long-term mortality. The underlying mechanism is usually inadequate blood flow
through a recanalized vessel or reocclusion. Vigorous medical therapy should be instituted, including
nitrates, beta-blockers, and calcium blockers, as well as aspirin and heparin. Most patients with
postinfarction angina -and all who are refractory to medical therapy - should undergo early catheterization
and revascularization by PTCA or CABG.
Right vntricular ifarction
Right ventricular infarction is present in one-third of patients with inferior wall infarction but is
clinically significant inless than 50% of these. It presents as hypotension with relatively preserved left
ventricular function and should be considered whenever patients with inferior infarction exhibit signs of
low cardiac output and raised venous pressure.
Hypotension is often exacerbated by medications that decrease intravascular volume or produce
venodilation, such as diuretics, nitrates, and narcotics. Right atrial pressure and jugular venous pulsations
are high, while PCWP is normal or low and the lungs are clear.
The diagnosis is suggested by right precordial ST segment elevation using V1and leads to the right
of the sternum corresponding to the location of V3 and V4. The diagnosis can be confirmed by
echocardiography or hemodynamic measurements. When hypotension is present, hemodynamic
measurements are necessary to monitor therapy.
Treatment consists of fluid loading to improve left ventricular filling; inotropic agents may also be
useful.
Mechanical defects.
Partial or complete rupture of a papillary muscle or of the interventricular septum occurs in less
than 1% of acute myocardial infarctions and carries a poor prognosis. These complications occur in both
anterior and inferior infarctions, usually 3-7 days after the acute event. They are detected by the
appearance of a new systolic murmur and clinical deterioration, often with pulmonary edema.
The two lesions are distinguished by the location of the murmur (apical versus parasternal) and by
Doppler echocardiography. Hemodynamic monitoring is essential for appropriate management and
demonstrates an increase in oxygen saturation between the right atrium and pulmonary artery in
ventricular septal defect and, often, a large v wave with mitral regurgitation.

Treatment by nitroprusside and, preferably, IABC reduces the regurgitation or shunt, but surgical
correction is mandatory. In patients remaining hemodynamically unstable or requiring continuous
parenteral pharmacologic treatment or counterpulsation, early surgery is recommended, though mortality
rates are high (15% to nearly 100%, depending on residual ventricular function and clinical status).
Patients who are stabilized medically can have delayed surgery with lower risks (10-25%).
Myocardial rupture.
Complete rupture of he left ventricular free wall occurs in less than 1% of patients and usually
results in immediate death. It occurs 2-7 days postinfarction, usually involves the an- terior wall, and is
more frequent in older women. Incomplete or gradual rupture may be sealed off by the pericardium,
creating a pseudoaneurysm. This may be recognized by echocardiography, radionuclide angiography, or
left ventricular angiography, often as an incidental finding. It demonstrates a narrow-neck connection to
the left ventricle. Early surgical repair is indicated, since delayed rupture is common.
Left ventricular aneurysm
Ten to 20 percent of patients surviving an acute infarction develop a left ventricular aneurysm, a
sharply delineated area of scar that bulges paradoxically during systole. This usually follows anterior Q
wave infarctions. Aneurysms are recognized by persistent ST segment elevation (beyond 4 -8 weeks), and
a wide neck from the left ventricle can be demonstrated by echocardiography, scintigraphy, or contrast
angiography. They rarely rupture but may be associated with arterial emboli, ventricular arrhythmias, and
congestive heart failure. Surgical resection may be performed for these indications if other measures fail.
The best results (mortality rates of 10-20%) are obtained when the residual myocardium contracts well
and when significant coronary lesions supplying adjacent regions are bypassed.
Pericarditis.
The pericardium is involved in approximately 50% of infarctions, but pericarditis is often not
clinically significant. Twenty percent of patients with Q wave infarctions will have an audible friction rub
if examined repetitively. Pericardial pain occurs in approximately the same proportion after 2-7 days and
is recognized by its variation with respiration and position (improved by sitting). Often, no treatment is
required, but aspirin (650 mg every 4-6 hours) or indomethacin (25 mg three or four times daily) will
usually relieve the pain. Anticoagulation should be avoided, since hemorrhagic pericarditis may result.
From 1 to 12 weeks after infarction, Dressier's syndrome (post-myocardial infarction syndrome)
occurs in less than 5% of patients. This is an autoimmune phenomenon and presents as pericarditis with
associated fever, leukocytosis, and, occasionally, pericardial or pleural effusion. It may recur over months.
Treatment is the same as for other forms of pericarditis. A short course of corticosteroids may help if
nonsteroidal agents do not relieve symptoms.
Infarct extension and postinfarction ischemia.
Recurrent infarction in the region of infarction (infarct extension) in the first 10-14 days occurs in
approximately 10% of patients. It may be associated with prolonged or intermittent episodes of chest
pain. In many cases, the process is relatively silent, being detected on routine ECG, by laboratory testing,
or by onset or worsening of heart failure. Infarct extension is at least twice as common in non-Q wave
infarcts and is more likely to occur after successful thrombolytic therapy owing to residual jeopardized
myocardium. Diltiazem has been shown to reduce the rate of extension following non-Q wave infarction.
Approximately 30% of patients will have angina postinfarction. This is more common in patients
with angina prior to infarction and in non-Q wave infarction. Postinfarction angina is associated with
increased short- and long-term mortality. The underlying mechanism is usually inadequate blood flow
through a recanalized vessel or reocclusion. Vigorous medical therapy should be instituted, including
nitrates, beta-blockers, and calcium blockers, as well as aspirin and heparin. Most patients with

postinfarction angina -and all who are refractory to medical therapy - should undergo early catheterization
and revascularization by PTCA or CABG.
Cardiac thromboembolism
Develop in up to 40% of patients with large anterior transmural MIs
If left untreared, up to 15% of thrombi will dislodge and result in symptomatic embolic event.
More common within first few months following infarction. Management. Involves anticoagulation with
warfarin for 6 months if there is a documented intracavitary thrombi; and 3 months prophylactically.
Left ventricular aneurysm
Develops following a large transmural anterior infarct
Can often be palpated as a dyskinetic region adjacent to the apical impulse, may also
auscultate a S3 and observe signs of heart failure
A non-specific EKG marker is persistent ST elevation that persists weeks following
infarction
Ventricular tachycardia is commonly associated with an aneurysm
Increases risk of thromboembolism (~5%), with the risk of being greatest within the first
few weeks
Predisposes to ventricular arrhythmias
Pseudoaneurysm
Rare
Myocardial rupture is sealed off by surrounding adherent pericardium
May progressively get larger, but maintains a narrow neck
Most common symptoms are heart failure, chest pain, and dyspnea, but very few report
symptoms (< 10%)
Psychosocial Complications
~20 50% have anxiety, depression, denial, hostility, and feel socially isolated
15 20% of patients hospitalized may have a major depressive disorder
Compound effects result from lifestyle and socioeconomic factors and can result in poor
adherence to therapies which subsequently lead to poor outcomes