This presentation is made to help students prepare for EDIC exam. this is board review for any exam for critical care examining acute MI, myocardial infarction, acute coronary syndrome.
2. Definition
• Acute coronary syndrome (ACS) refers to a spectrum of clinical
presentations ranging from those for
• ST-segment elevation myocardial infarction (STEMI)
• non–ST-segment elevation myocardial infarction (NSTEMI)
• unstable angina.
• It is almost always associated with rupture of an atherosclerotic
plaque and partial or complete thrombosis of the infarct-related
artery. (MYOCARDIAL ISCHEMIA)
3. Unstable Angina
• Unstable angina (UA) - Ischemic type chest pain, which is of recent
origin, is more frequent, severe, or prolonged than the patient’s usual
angina; is more difficult to control with drugs; or is occurring at rest
or on minimal exertion. Cardiac biomarkers are not elevated.
4. Myocardial Infarction
• Myocardial infarction – Ischemic symptoms with evidence of raised
cardiac biomarkers. Acute myocardial infarction (AMI) may be further
categorized as:
• STEMI – Myocardial infarction with ST-segment elevation on the
presenting or subsequent 12-lead electrocardiograms (ECGs).
• Non-STEMI (NSTEMI) – Myocardial infarction occurring without ST
segment elevation on presenting or subsequent 12-lead ECGs.
5. Clinical classification of different types of myocardial infarction
Type 1 Spontaneous myocardial infarction related to ischaemia due to a primary
coronary event such as plaque erosion and/or rupture, fissuring, or
dissection
Type 2 Myocardial infarction secondary to ischaemia due to either increased
oxygen demand or decreased supply – for example coronary artery
spasm, anaemia, arrhythmias, or hypotension
Type 3 Sudden unexpected cardiac death, including cardiac arrest, often with
symptoms suggestive of myocardial ischaemia, accompanied by
presumably new ST elevation, or new LBBB (left bundle branch block), or
evidence of fresh thrombus in a coronary artery by angiography and/or at
autopsy, but death occurring before blood samples could be obtained, or
at a time before the appearance of cardiac biomarkers in blood
Type 4a Myocardial infarction associated with percutaneous coronary
intervention
Type 4b Myocardial infarction associated with stent thrombosis as documented by
angiography or autopsy
Type 5 Myocardial infarction associated with coronary artery bypass grafting
7. Risk stratification and triage
• History and physical
• ECG
• Cardiac Enzymes
• Echocardiography may be required
Diagnosis is made from following
• STEMI
• NSTEMI
• ST Depression suggestive of acute ischemia
• Non coronary chest pain or stable angina
• Stable angina for outpatient treatment
9. Immediate action
• 12-lead ECG (within 5 minutes of arrival).
• Oxygen via face mask or nasal cannula.
• Venous access. Blood is drawn for cardiac biomarkers, biochemical
and haematological work-up.
• Sublingual nitroglycerin 0.4 mg (repeated once or twice as necessary)
may have beneficial effects.
• Side effects include hypotensive reactions and a hypotensive bradycardic
response (Bezold-Jarisch Reflex).
10. Immediate action
• Analgesia. Often oxygen, nitroglycerin and lessening of anxiety by
reassurance, are sufficient. If not, administer small incremental
boluses of intravenous morphine (1–2 mg), repeated until pain is
relieved.
• Aspirin 160–325 mg should be chewed Simple inexpensive therapies
can and swallowed on arrival. have dramatic effects on survival
11. Immediate action
• Clopidogrel, a thienopyridine that blocks the platelet ADP receptor,
has been shown to improve outcomes when added to TIMI = aspirin
for both patients with STEMI [COMMIT-CCS-2, CLARITY-TIMI 28] and
NSTEMI [CURE]. Most patients should be given a loading dose of
clopidogrel of 300–600 mg, especially if an invasive strategy is
planned. Prasugrel, another thienopyridine, has also been shown to
be effective in this setting [TRITON-TIMI38].
12. Immediate action
• Beta-adrenergic blockers should be used in patients without evidence
of heart failure or hypotension, and should preferentially be
administered orally.
• Pulmonary oedema, if present, is treated with upright posture,
intravenous frusemide (furosemide in US) (40 mg i.v.), sublingual or
intravenous nitroglycerin and if severe, with non-invasive ventilation
or CPAP.
13. STEMI
• STEMI patients presenting to a hospital with PCI (Percutaneous
transluminal coronary interventions) capability should be treated with
primary PCI within 90 minutes of first medical contact.
• STEMI patients presenting to a hospital without PCI capability and
who cannot be transferred to a PCI centre for intervention within 90
minutes of first medical contact should be treated with fibrinolytic
therapy within 30 minutes of hospital presentation, unless
contraindicated.
14. High Risk Patients
• Patients who have received thrombolytic therapy should be
considered for transfer to a PCI-capable centre, depending on risk
profile.
• High risk can be defined by clinical features
• presentation in congestive heart failure
• haemodynamic criteria (SBP <100 mmHg, HR >100 bpm),
• size of infarction (anterior ST elevation >2 mm in two or more contiguous
leads),
• RV involvement,
• or LV dysfunction (EF <35%).
15. Right ventricular infarction
• What are the clinical features of right ventricular infarction and why
is it important to make this diagnosis?
• marked elevation of the jugular venous pressure (JVP), usually with
clear lungs and low or normal wedge pressure.
• Recognition of RV infarction is important because decreasing filling
pressures in this setting may precipitate hypotension and, conversely,
hypotension may respond to judicious fluid administration.
19. Troponins
• Troponins are very sensitive markers of cardiac injury, more sensitive
than traditional markers such as CK.
• About 33% of patients with ACS and normal CK (and no ECG changes
of infarction) have elevated cTn. Such patients with isolated elevated
cTn are, however, four times more likely to suffer further infarction or
death in the next 30 days than those with both normal CK and normal
cTn.
24. False trop Elevation
• Myocarditis
• following cardiac surgery
• cardiac trauma
• Sepsis
• renal insufficiency
• massive pulmonary embolism (reflecting right ventricular injury).
25. False Trop Elevation
• Elevated troponin levels are also common in ICU populations.
Although initially considered as ‘false positives’, many of these are
now thought to be reflective of disease processes which secondarily
involve the myocardium or induce a supply–demand mismatch e.g.
vasoconstrictor use, overwhelming bacterial sepsis, multiple organ
failure, renal failure and cerebrovascular catastrophes.
26. Role of Echocardiography in ACS
• Echocardiography detects regional wall motion abnormalities and/or
loss of wall thickening, which often precede overt ECG changes. These
can help confirm the diagnosis of MI. It is also useful in the diagnosis
of patients with late presentation or with LBBB, although clinical
context is required to determine the timing of infarction.
• Absence of regional wall motion abnormality suggests that ischaemia
is not significant
• Echocardiography may be useful for excluding aortic dissection or
pericardial effusion.
27. Role of Echocardiography in ACS
• Echocardiography provides a bedside assessment of LV function and
infarct size, and can also confirm RV infarction.
• It is particularly useful in the diagnosis of complications of MI,
including acute mitral regurgitation, VSD formation, myocardial
rupture, pericardial effusion, and infarct expansion.
• Echocardiography may also be used in the management of infarction.
Transoesophageal echocardiography may have a role in the therapy of
cardiogenic shock, and may help guide volume therapy.
28. How to separate ‘high risk’ from ‘lower risk’
NSTEMI patients?
• Features which suggest high risk in non-ST elevation ACS and hence
the need for more ‘aggressive’ therapy and investigation include:
• Angina refractory to medical therapy
• ST-segment depression, especially when dynamic
• Elevated troponin
• Ischaemia associated with heart failure, haemodynamic instability or
arrhythmia
• Age, past history of coronary events, diabetes, hyperlipidaemia,
smoking.
29. NSTEMI is not benign
• Non-ST-segment elevation ACS should not be considered a benign
condition. Approximately 10% of patients presenting with a non-ST
elevation ACS will die or have myocardial infarction at six months,
with half of these events occurring in the first week of presentation.
With aggressive management, many of these events may be
preventable.
30.
31. Pathophysiology
Major risk factors
Family history
Increased LDL (low-density lipoproteins)
cholesterol
Cigarette use Low HDL cholesterol
Diabetes Obesity
Hypertension
Elevated CRP (C-reactive protein) (High
Sensitivity)
32. Pathophysiology
• Atherosclerotic plaques are composed of a lipid core, which includes
cholesterol, oxidised low-density lipoproteins (LDL), macrophages, and
smooth muscle cells, covered by a fibrous cap.
• ‘Vulnerable plaque’ is often rich in lipid and covered by a thin fibrin
cap. Plaque rupture or fissuring exposes thrombogenic lipid and
collagen, which are potent activators of platelets. Plaque erosion
activates coagulation pathways and also activates adherent platelets.
33.
34. Pathophysiology
• Inflammatory processes play an important role in rendering plaques
vulnerable to rupture, as they both activate metalloproteinases that
degrade collagen in the fibrous cap and inhibit synthesis of new
collagen.
• Lipid-lowering agents may stabilise plaque not only by lowering
plaque cholesterol but also through lipid-independent (‘pleiotropic’)
anti-inflammatory effects.
35. White Thrombus
• ‘White thrombus’ results from platelet accumulation but is seldom
totally occluding. Activated GP IIb/IIIa receptors cross-link fibrinogen
between activated platelets, promoting the formation of platelet
thrombi. Activation of the GP IIb/IIIa receptor is the final common
pathway leading to thrombin activation. Platelet embolism
downstream may result in micro-infarction, evidenced by elevated
troponin.
36. Treatment of White Thrombus
• ‘White thrombus’ (platelet-rich) formation is best limited by the use
of antiplatelet agents. These may inhibit cyclo-oxygenases (e.g.
aspirin), ADP receptor-mediated platelet aggregation (e.g.
clopidogrel, prasugrel) or GPIIb/IIIa receptors (e.g. abciximab,
tirofiban, eptifibatide).
37. Red Thrombus
• Activation of coagulation pathways by exposed lipid and fibrin as
well as by the now activated platelets, leads ultimately to thrombin
activation and the laying down of fibrin clot. Red cells are enmeshed
in this so-called ‘red thrombus’ complex, which surrounds the ‘white
thrombus’.
• Sudden artery occlusion by thrombus may thus complicate even only
moderate sized plaques. Vessel vasoconstriction and spasm may also
potentiate ischaemia.
38. Treatment of Red Thrombus
• ‘Red thrombus’ may be addressed by fibrinolytic agents or anti-
thrombin therapy. Current thrombolytic agents lyse fibrin and red
cell thrombus, but paradoxically may increase thrombin activation.
Concomitant administration of anti-thrombin agents (e.g. heparins)
may limit thrombin activation. Spontaneous lysis of red thrombus
may occur, but this is usually too late to preserve myocardial tissue.
39.
40.
41. Pathophysiology correlated with presenting
syndrome
• STEMI is generally due to total occlusion of a coronary artery
superimposed on a vulnerable plaque, leading to myocardial damage
in its area of distribution. The extent of loss of muscle tissue may be
reduced by timely restoration of coronary flow.
•
42. Pathophysiology correlated with presenting
syndrome
• NSTEMI and Unstable Angina are usually caused by an imbalance between
myocardial oxygen supply and demand, which may be due to one or more
of the following causes:
• Non-occlusive thrombus developing on a pre-existing plaque (the most frequent
cause). Arterial inflammation or infection can predispose to plaque rupture.
• Dynamic obstruction – spasm of an epicardial artery or intramural vasoconstriction.
• Progressive coronary narrowing without spasm or thrombus. May be due to
progressive atherosclerosis or restenosis after a PCI.
• Secondary UA (‘demand ischaemia’). Patients with chronic atherosclerotic
narrowing are subjected to increased myocardial oxygen demand (fever,
tachycardia) or reduced oxygen delivery (hypotension, anaemia).
•
44. STEMI restoration of coronary patency
• Therapy to restore patency should be considered for all patients
presenting within 12 hours after the onset of STEMI.
• Restoration of patency:
• Reduces mortality and prolongs survival
• Preserves LV function
45. Revascularization on the basis of ECG
ST-segment elevation in 2 or more contiguous leads
>2 mm in chest leads (V2–V6)
or
>1 mm in limb leads (I, aVL, II, III, aVF)
Or
New-onset LBBB (include presumed new-onset)
Or
Posterior infarction (Dominant R wave and ST depression 2 mm in V1–V2)
Or
Presentation 12–24 hours after onset of ACS with continuing pain and evidence of
evolving infarction
46. Strategies to achieve coronary patency
Strategies to achieve coronary patency (reperfusion) can include:
• Fibrinolytic (thrombolytic) therapy
• Percutaneous transluminal coronary interventions (PCI) e.g.
angioplasty
• Coronary artery bypass grafting (CABG).
47. Factors that influence treatment choice and
outcome
• Skill and expertise of admitting hospital
• Time since onset of symptoms
• Time required for transfer to a cardiac catheterisation laboratory
skilled in performing PCI
• Patient age
• Comorbid illness (particularly risk of bleeding and stroke) Previous
surgery
• Haemodynamic status
48. TRANSFER-AMI after thrombolysis for STEMI
• Data from the TRANSFER-AMI study suggest that high-risk patients
who received thrombolysis for STEMI should be considered for
transfer to a PCI capable facility immediately after fibrinolysis without
waiting to see whether reperfusion is successful or not. This resulted
in a reduction in the combined endpoint of death, MI, heart failure,
severe recurrent ischaemia, or shock to 11.0% compared to 17.2% in
patients transferred only for rescue PCI.
49. Situations in which PCI is clearly superior to
thrombolysis
• Contraindications to thrombolytic therapy
• Cardiogenic shock
• Severe heart failure
• Haemodynamically significant ventricular arrhythmias.
50. Situations in which PCI may be preferable to
thrombolysis
• Elderly patients (age >75 years)
• Large anterior infarction
• Prior myocardial infarction or prior coronary artery bypass grafting
• High bleeding risk.
51. Other indications for angioplasty in AMI
• Rescue PCI is indicated for patients who fail thrombolytic therapy,
although the initial success rate is lower than that of primary
angioplasty, reocclusion is more common, and mortality is higher.
• Limited available data suggests a reduction in the combined
endpoints of death or heart failure at 30 days with rescue PCI.
52. Thrombolysis
• Thrombolytic therapy should be given as early as possible in the
emergency department. Initial reperfusion is expected in
approximately 80% of patients if given within two hours of symptom
onset.
• A goal is ‘door to needle time’ of less than 30 minutes. Delay is
associated with excess mortality.
• Mortality- Relative reduction in death rate at 35 days of about 21%
(absolute reduction approximately 2%, or 20 deaths per 1000 patients
treated).
54. Aspirin
• Aspirin (160–325 mg chewed or swallowed) should be given as soon
as possible after the diagnosis of ACS or MI and is usually continued
long term. It does not appear to increase bleeding and the benefit is
still present after 10 years.
55. Clopidogrel
• Clopidogrel (300–600 mg loading dose and 75 mg maintenance dose
for at least two weeks post MI)
• adenosine diphosphate–receptor antagonist, a class of oral
antiplatelet agents that block the P2Y12 component of the adenosine
diphosphate receptor and thus inhibit the activation and aggregation
of platelets in a manner different from that of aspirin.
• Prasugrel is a new, relatively potent, thienopyridine being studied
with which there is still relatively limited, broad, clinical experience.
•
56. Dual antiplatelet therapy
• Dual platelet inhibition with aspirin and clopidogrel has been shown
to reduce morbidity and mortality in patients with ST elevation MI
receiving thrombolysis (CLARITY-TIMI 28), rescue PCI after failed
thrombolysis (CLARITY-PCI), PCI for ACS (CURE), as well as in a wide-
range of patients, some of whom were not treated with reperfusion
therapy (COMMIT-CCS-2).
57. ABSOLUTE RELATIVE
(Advisory following clinical consideration)
Previous haemorrhagic stroke Severe hypertension (180/110 mmHg) not controlled
after sedation and analgesia
Other stroke or
cerebrovascular accident 6 months
Oral anticoagulation therapy (INR >2.5); known bleeding
diathesis
Intracranial neoplasm Recent major trauma, surgery ( 4 weeks) including head
trauma
Active internal bleeding 2 weeks (menses excluded) Previous allergic reaction to drug to be used
Aortic dissection, known or suspected Traumatic CPR
Active peptic ulcer disease
Pregnancy
Recent streptokinase. Use different agent (risk of allergy,
antibodies may reduce effectiveness)
History of prior CVA or intracerebral pathology not
covered in contraindications
Chronic hypertension
58. Anticoagulation
LMWHs advantages
• Predictable, consistent pharmacokinetic profiles and anticoagulant
response (no monitoring of the aPTT necessary).
• Enhanced anti-Xa activity and are less affected by platelet factors.
Convenience of subcutaneous administration (no i.v. line).
• Lower incidence of thrombocytopenia (HITT), skin necrosis,
hypersensitivity.
60. Glycoprotein IIb/IIIa inhibitors
• These agents override the platelet activation caused by plasminogen
activators, improving patency rates and allowing better reperfusion of
small vessels beyond the occluding thrombus. They may have a role in
STEMI when acute interventions such as percutaneous transluminal
coronary angioplasty (PCI) and coronary artery stenting are
performed
• abciximab, tirofiban and eptifibatide.
61. Beta Blockers
• Mortality benefit
• All patients without contraindications (pulmonary oedema, asthma,
hypotension, bradycardia, advanced atrioventricular block) should be
treated with β-blockers within 24 hours of the onset of symptoms.
63. Use of right heart catheterisation and echocardiography in
diagnosis of complications of MI
64. Use of ionotropes
• Dobutamine, a selective β1-adrenergic receptor agonist, can improve
myocardial contractility and increase cardiac output, and it is the
initial agent of choice in patients with a low-output syndrome and
systolic blood pressures >90 mmHg. Dobutamine may exacerbate
hypotension in some patients (reconsider hypovolaemia if this occurs)
owing to its vasodilatory effects, and it can precipitate
tachyarrhythmias. Adrenaline increases both blood pressure and
cardiac output, and so may be considered when systolic pressures are
less than 80 mmHg, but can precipitate arrhythmias and may worsen
ischaemia.
65. Use of ionotropes
• Milrinone, a phosphodiesterase inhibitor that increases intracellular
cyclic AMP by mechanisms not involving adrenergic receptors, has
less prominent chronotropic and arrhythmogenic effects compared to
catecholamines. It does, however, have the potential to cause
hypotension and has a long half-life; in patients with tenuous clinical
status, its use is often reserved for situations in which other agents
have proven ineffective. Milrinone is started without a bolus in this
setting, and sometimes adjunctive vasopressor support is required.
66. Use of ionotropes
• Levosimendan, a calcium sensitizer, has both inotropic and
vasodilatory properties, and does not increase myocardial oxygen
consumption. Several relatively small studies have shown
haemodynamic benefits with levosimendan in cardiogenic shock after
MI, but survival benefits with use of levosimendan have not been
shown in either cardiogenic shock or acute heart failure.
Levosimendan has the potential to cause hypotension and thus
should be used with caution in patients with cardiogenic shock.
67. IABP
• IABP use reduces systolic afterload and augments diastolic perfusion
pressure, improving cardiac output and coronary blood flow. These
beneficial effects, in contrast to those of inotropic or vasopressor
agents, occur without an increase in oxygen demand. IABP alone does
not increase survival, but is an essential support mechanism to allow
definitive therapeutic measures to be undertaken.
69. How to give ongoing and discharge care
(secondary prevention) and evaluate outcome
Aspirin
• Aspirin should be given daily and continued indefinitely, unless there
are strong contraindications. In the first two years after MI, aspirin
therapy results in an absolute decrease of approximately 36 vascular
events (vascular death, nonfatal MI or stroke) for every 1000 patients
treated. Doses ranging from 75 to 325 mg have been proven effective.
70. Thienopyridines
• Whether the patient has suffered STEMI or NSTEMI, and whether the
patient underwent reperfusion therapy with PCI, CABG, or
thrombolysis, discharge medication should include clopidogrel 75 mg
daily for at least one month and preferably for 12 months. If a drug-
eluting stent was placed, clopidogrel should be continued for at least
one year, if not longer.
71. • Beta blockers
• β-blockers significantly reduce the incidence of sudden and non-
sudden cardiac death in survivors of MI. Benefit is prolonged and is
most marked in high-risk patients e.g. extensive anterior infarction.
This benefit extended to patients previously thought to have
contraindications to β-blockers (such as heart failure, pulmonary
disease or old age)
72. • ACE inhibitors and ARBs
• ACE inhibitors significantly reduce mortality in high-risk patients when
commenced during recovery from MI (SAVE trial). Patients with
anterior myocardial infarction and ejection fraction <40% maintained
on long-term ACE inhibitor therapy, may experience a 20% relative
reduction in mortality and a significant reduction in the incidence of
heart failure as evidenced by the HOPE and EUROPA studies.
Angiotensin receptor blockers (ARBs), specifically candasartan and
valsartan, have been shown to be effective alternatives to ACE
inhibitors
73. • Lipid lowering agents
• A ‘statin’ should be started in all patients following myocardial
infarction. Lowering cholesterol following MI (whether initially
elevated or not) results in a decrease in mortality and re-infarction
74. Other anti ischemic agents
• Nitrates may be continued where angina is refractory to β-blockade
• Ranolazine should be considered for refractory angina
• Routine use of calcium antagonists does not improve outcome
• Agents that increase heart rate (e.g. dihydropyridines) may increase
death and re-infarction
• Agents that reduce heart rate (verapamil, diltiazem) have a neutral
effect on mortality but may reduce re-infarction rates.
75. Anti-arrhythmic agents
• Anti-arrhythmic therapy is not routinely continued. Hypokalaemia
should be corrected. Empirical magnesium therapy has not been
proven of value; however it is advised to correct hypomagnesaemia,
especially in patients with ventricular ectopy. Amiodarone in low
doses (200 mg daily) may reduce mortality in selected patients;
however, definitive trials are awaited and it has significant side effects
76. Warfarin
• Warfarin may be given to patients with large anterior infarction,
especially those with suspected or demonstrated apical thrombus.
High dose regimens have been proven better than control for
decreasing re-infarction, stroke and mortality after MI. Moderate and
high dose regimens have given outcomes comparable to but not
superior to aspirin. Warfarin therapy (target INR of 2.5–3.5) should be
considered in patients with ACS and true aspirin allergy
77. LIFE STYLE ADVICE
• Lifestyle advice is most important. All patients should cease smoking
and receive advice on exercise and diet. Referral to a cardiac
rehabilitation programme is also recommended
• Aggressive treatment of hypertension and diabetes is required in any
patient with coronary artery disease
