Acute coronary syndromes Flashcards by Namood Waseem

What are some causes of chest pain?

Blood clot in the lungs (PE)
Angina
Myocardial infarction – most severe

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Why is it important to define the type of IHD (ischaemic heart disease)?

Need to know if it’s stable Angina or Acute Myocardial Infarction (needs rapid intervention)
• Treatment
• Prognosis
• Management

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What is considered in the assessment of IHD?

Medical history
Risk factors
Presenting signs and symptoms
ECG
Biomarkers
Imaging/scans

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What 2 major diseases is coronary heart disease divided into it?

Acute coronary syndromes

- Chronic ischaemic heart diseases

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Examples of chronic ischaemic heart diseases?

Stable angina: pain gets worst with exertion
Variant angina: due to vascular spasm of the vessels
Silent myocardial ischaemia: fewer symptoms, low oxygen levels, not feeling chest pain

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Examples of acute coronary syndrome?

Unstable angina: pain even without exertion, ECG and cardiac marker elevation differentiates it
Non ST-segment elevation MI
ST-segment elevation MI: more serious than NON ST-segment elevation MI

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How is acute cardiac ischemia caused?

Plaque disruption or erosion
Thrombus formation with or without embolization
acute cardiac ischemia happens

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What is the difference between ST segment elevation and non-ST segment elevation?

No necrosis (troponin markers are normal) – it’s unstable angina
If there is necrosis – it’s a non ST segment elevation
If there’s markers of necrosis and the ST segment elevation on ECG, it’s ST segment elevation

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What is seen in unstable angina patients?

More flow in unstable angina patients – flow is reduced but not enough to increases markers

• The lumen is wider than non-ST segment elevation MI/ST segment elevation MI

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What is seen in non-ST segment elevation?

In non-ST segment elevation there’s a significant reduction in lumen – thrombus and platelet activation aggregation is more significant

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What is seen in ST segment elevation?

In ST segment elevation – full occlusion of vessel

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What are the treatment aims for acute coronary syndromes?

Relieve symptoms
Improve survival
Minimise cardiac risk

Major aim of treatment should be to facilitate a return to normal activities

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What are the methods of recanalisation for acute myocardial infarction?

With ST segment 2 options:

– PCI (percutaneous coronary intervention), balloon angioplasty with stent
– thrombolytic therapy, usually if there’s no access to PCI/primary angioplasty

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What happens if there is no recanalization after thrombolytic treatment?

If there’s no recanalization after thrombolytic treatment, delayed/rescue angioplasty is used

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What is used to monitor and manage the patients?

Cardiac CT angiography

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What are the treatments of acute coronary syndromes?

• Surgical/Intervention
o Balloon angioplasty
o Stent
o Coronary bypass

• Pharmacological treatment

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What is the initial pharmacological approach for ST-segment elevation myocardial infarction?

Given O2 (2-4 L/min) if patient has short of breath
IV diamorphine with IV anti-emetic (metaclopramide or cyclizine) – pain relief
Aspirin and Clopidogrel – anti-platelet
IV beta adrenergic antagonists - beta blocker

What are some thrombolytics/fibrinolytics used for treatment?

Streptokinase - cheap
Urokinase
Tissue plasminogen activators – mainly used

What are 2 plasminogen activators?

Tissue plasminogen activator (tPA)

- urokinase plasminogen activator (uPA)

What does thrombin do?

converts fibrinogen into fibrin which cross links with other fibrin – forms net

Describe tissue plasminogen activator-mediated thrombolysis?

Tissue plasminogen activator (tPA) and urokinase plasminogen activator (uPA) are plasminogen activators – convert plasminogen to plasmin (potent proteolytic enzyme that degrades cross linked fibrin net into small pieces)
Binding sites on tPA and plasminogen for fibrin – makes fibrinolysis very specific to fibrin formation/where the clot is

What is the normal conformation for tPA and why is it kept in that conformation normally?

tPA normally kept in inactivate conformation by plasminogen activator inhibitor type 1 (tPAI1)

tPA-PAI1 complex tethered to EC – prevents tPA from activating circulating plasminogen
when there’s fibrin tPA has greater affinity for it, can disassociate from its complex and bind to fibrin and plasminogen and form the degradation products

What is a plasmin inhibitor?

a2 antiplasmin

Difference between tissue plasminogen activator and streptokinase (which is also a plasminogen activator)?

SK is bacterial (beta-haemolytic streptococci) possible immune recognition
SK will bind circulating plasminogen not associated with fibrin – generalised plasmin generation aka systemic plasminogen activation
SK is less fibrin specific, more systemic plasminogen activation and can cause bleeding
Antibodies (because it’s bacterial) generated that thwart subsequent doses and possible allergic reaction

What is mechanism of action of Streptokinase?

* SK binds with free circulating plasminogen/plasmin | * Forms an active complex (with plasminogen and plasmin) that can convert additional plasminogen to plasmin

What are structural differences between Alteplase and newer formulations of tPA (Reteplase and Tenecteplase)?

* Alteplase (Actilyse/Activase) – full length tPA * Reteplase – derivative of tPA * Tenecteplase – modification of tPA

What are kringle domains?

Kringles are triple-looped, disulphide cross-linked domains found in a varying number of copies, in some serine proteases and plasma proteins: * Tissue plasminogen activator (tPA) (2 copies) * Urokinase-type plasminogen activator (1 copy)

What are the different functional domains of tPA/alteplase (rtPA)?

* Finger domain at the n-terminus * Growth factor domain/epidermal growth factor domain * 2 Kringle domains – each is a triple looped structure held by further bonding * Proteolytic domain

What is the function of the finger and growth factor domains?

* these structural units have high affinity for fibrin – give the specificity for fibrin * have low affinity for receptor binding sites on EC – they bind loosely to EC cells

What is the function of the kringle domains?

* Kringle 1: involved in clearance – through the liver the molecule gets cleared by kringle 1 unit cause it had some specific binding sites * Glycosylation of kringle 1 domain cause of side chains * Kringle 2: interacts with PAI-1 * There’s also some fibrin binding * Kringle 2 leads onto proteolytic domain

What is the function of the proteolytic domain?

* Where the catalytic activity of the protein is located * Where plasminogen is activated into plasmin * Interactions with PAI-1

What is the structure of reteplase (r-PA)?

* Only has Kringle 2 domain and protease domain * Deletion of finger region, EGF-like domain and kringle 1, & carbohydrate side chains * Hepatic elimination of the molecule is reduced – cause kringle 1 domain is removed * Plasma half-life is increased to 14–18 minutes (versus 3–4 minutes with alteplase) * Diminished fibrin binding

What is the structure of Lanoteplase (nPA)?

* Only has 2 kringle domains and protease domains | * Not used clinically

What is the structure of Tenecteplase?

* Has all of the domains but has modifications * Modified glycosylation residues/glycosylation side chains binding sides in K1 * Asn-103 for Thr * Gln-117 for Asn = prolonged half-life and glycosylation prevented * 4 alanine substitutions at 296-299 in Protease domain = enhanced fibrin specificity and resistance to PAI-1 inhibition, reduced systemic plasmin activation

What is really critical in acute coronary syndrome treatment?

Time from onset and severity of symptoms is critical * Arrival to ECG: has to be 10 min of chest pain * Door-to-needle for thrombolysis: 20 min * Door-to-balloon time for PCI: 60 min

What are the pharmacological treatments for acute coronary syndrome?

go down in this order, starting from top * General myocardial oxygenation * Antiplatelet/Antithrombotic * Analgesia * Myocardial energy consumption * Coronary vasodilatation * Anticoagulation * Thrombolysis * Plaque stabilization

Surgical interventions for ACS?

* Reperfusion | * Re-vascularisation

Pros and cons of thrombolysis?

* 55-60% recanalisation of vessel within 90 mins * 5-15% risk of reocclusion * Worsening ventricular function * 1-2% risk of intracranial haemorrhage with 40% mortality * 15-20% of patients have a contraindication to thrombolysis

Pros and cons of angioplasty

* 95% recanalisation of vessel within 60 mins * No systemic fibrinolysis * Reduced rates of death, cerebrovascular events and re-infarction * Costly * Specialist facilities and staff

Long term management after a myocardial infarction?

* Smoking cessation * Physical activity * Diabetes management * Diet and weight reduction * Blood pressure control * Lipid management * Management of heart failure or LV dysfunction * Prevention of sudden death