Acute coronary syndrome for critical care exam

Acute Coronary Syndrome

ESICM Fakhir

14-3-2017

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)

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.

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.

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

Differential diagnosis• Aortic dissection• pericarditis • pulmonary embolus

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

Immediate evaluation• non-invasive blood pressure measurement• pulse oximetry• continuous ECG monitoring.

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).

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

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].

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.

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.

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%).

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.

Reasons of ST segment changes (STEMI on ECG)

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.

Risk scoring systems (benefit from intervention)• Grace scoring system

TIMI (Thrombolysis in Myocardial Infarction) scoring systems

False trop Elevation• Myocarditis• following cardiac surgery• cardiac trauma• Sepsis• renal insufficiency• massive pulmonary embolism (reflecting right ventricular injury).

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.

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.

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.

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.

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.

Pathophysiology Major risk factors

Family historyIncreased LDL (low-density lipoproteins) cholesterol

Cigarette use Low HDL cholesterol

Diabetes Obesity

Hypertension Elevated CRP (C-reactive protein) (High Sensitivity)

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.

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.

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.

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).

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.

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.

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. •

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).

•

MI can be complicated by Shock

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

Revascularization on the basis of ECGST-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

Strategies to achieve coronary patencyStrategies to achieve coronary patency (reperfusion) can include: • Fibrinolytic (thrombolytic) therapy • Percutaneous transluminal coronary interventions (PCI) e.g.

angioplasty • Coronary artery bypass grafting (CABG).

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

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.

Situations in which PCI is clearly superior to thrombolysis • Contraindications to thrombolytic therapy • Cardiogenic shock • Severe heart failure • Haemodynamically significant ventricular arrhythmias.

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.

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.

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).

Contraindications of thrombolysis• Absolute and relative

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.

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. •

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).

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

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.

early adjunctive treatments following STEMI

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.

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.

MANAGEMENT OF COMPLICATIONS • Arrhythmia • Post-infarction angina and infarct extension • Systemic embolisation • Haemodynamic instability • Ventricular free wall rupture• Ventricular septal rupture• Acute mitral regurgitation• Cardiogenic shock• Right ventricular infarction

Use of right heart catheterisation and echocardiography in diagnosis of complications of MI

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.

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.

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.

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.

DIASTOLE SYSTOLE

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.

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.

• 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)

• 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

• 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

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.

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

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

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

إالا البلاغ المبين وما علينا