Coronary Heart Disease PDF

Coronary Heart Disease (Coronary Artery Disease) Coronary Heart Disease Ischaemic heart disease Atherosclerosis Angina, Acute Coronary Syndrome (ACS) Coronary Circulation Oxygen Demand and Supply Ischaemia an inadequate blood supply to an organ or part of the body, especially the heart mu...

Coronary Heart Disease (Coronary Artery Disease) Coronary Heart Disease Ischaemic heart disease Atherosclerosis Angina, Acute Coronary Syndrome (ACS) Coronary Circulation Oxygen Demand and Supply Ischaemia an inadequate blood supply to an organ or part of the body, especially the heart muscles. Infarction death of tissue resulting from a failure of blood supply, Causes Atherosclerosis Embolus Vasospasm Vasculitis Risk factors for Atherosclerosis? BAD HEART B – BMI >30 A – Age > 65 D – Diabetes H- Hypertension E – Ethanol A – Altered lipids (autoimmune) R – Relatives T - Tobacco Atherosclerosis Summary Atherosclerosis 1. Damage to endothelial cells 2. LDL accumulation (tunica intima) 3. Monocytes attracted (cytokines / adhesion molecules) – macrophages 4. Foam cell production – release content 5. Smooth muscle cell proliferation LDL and HDL Reduction of Cholesterol Statins – mechanism of action Inhibition HMG CoA Reductase Acute Coronary Syndrome ACS Pathophysiology Symptoms Chest pain, left arm , jaw , heavy weight on chest (elephant on your chest) Diabetics can present as atypical – (neuropathy masks symptoms) – also elderly , post heart transplant Diaphoresis Feeling of impending doom Stable Angina Only on exertion Stable plaque Ischaemia – subendocardial (approx. 70% occlusion) ACS (Acute Coronary Syndrome) Unstable Angina Unstable Plaque (approx. 90% occlusion) Symptoms at rest Ischaemia - subendocardial NSTEMI - Non-ST-elevation myocardial infarction STEMI - ST-elevation myocardial infarction NSTEMI Subendocardial infarct Unstable plaque Thrombus formed (>90% occlusion) – long term ischaemia STEMI Transmural infarct Total occlusion ECG Prinzmetals Angina/ Variant Angina Not atherosclerosis Vasospasm EtOH, smoking, cocaine, female, triptans Usually at night Transmural Ischaemia Also see ST elevation, but troponins not increased Treatment – CCB, nitrates to vasodilation AVOID beta blockers esp. non selective Complications Post MI Arrhythmias Heart Failure Secondary MI Inflammation – Pericarditis Rupture Clot Formation - embolus Diagnosis Symptoms ECG – ST elevation (can get ST depression) – ECG can help with determining region affected Troponins/ CKMB – increased following infarct ECHO – abnormalities Catheterisation – both diagnostic and therapeutic (PCI) COAGULATION AND DRUGS Thrombus Formation Blood Clotting Formation of thrombus 1. Arterial thrombus: — Thrombus has large head, formed from platelets — Primary trigger of arterial thrombosis is rupture of an atherosclerotic plaque (seen in yellow) Vessel wall Endotheliu Thrombus in the lumen of m a coronary artery Thrombus Rupture of plaque Atherosclerotic plaque Necrotic Foam core Adapted from © Can Stock Photo cells / megija — Mainly treated with antiplatelet drugs Formation of thrombus 2. Venous thrombus: — Thrombus consists of a fibrin web enmeshed with red blood cells and platelets — Tail can break off giving rise to embolisms A thromboembolus filling Abnormal blood a pulmonary artery flow Altered vessel Increased coagulabilit erythrocytes wall y Adapted from © Can Stock Photo / alila — Mainly treated with anticoagulant drugs Platelet Activation Treatment 1. Antiplatelet Drugs ASPIRIN (ASA) Cyclooxygenase inhibitor Clopidogrel ADP Inhibitor P2Y12 Antagonist Pro Drug Also Ticagrelor Prasugrel Abciximab, eptifibatide, tirofiban Inhibit GPIIb/IIIa https://doctorlib.info/pharmacology/illustrated/illustrated.files/image156.jpg Dipyridamole Decreases adenosine uptake Inhibits phosphodiesterase Treatment 2. Anticoagulant Drugs Coagulation Cascade https://i0.wp.com/ pocketdentistry.com /wp-content/ uploads/2017/08/ image00247.jpeg?  Heparin Antithrombin (ATIII) Is a serine protease inhibitor produced (naturally) by the liver Heparin binding increases Antithrombin activity (inhibitor) Antithrombin inhibits proteases on the contact activation pathway (intrinsic pathway): the activated forms of: Factor X (Xa) Factor IX (IXa) Factor XI (XIa) Factor XII (XIIa) Factor II (Thrombin or IIa) is inhibited via a ternary complex (heparin-ATIII-Thrombin) At least 18 saccharide units (unfractionated Heparin) Blood clotting cascade Extrinsic Intrinsic pathway pathway Tissue damage Contact Hepari VII VIIa n AT XII XI a I III Hepari XI X n AT a I Hepari IIIIX I n AT a X III Hepari X X a n AT III XIII II II (Thrombi (Prothrombi a n) n) Hepari XIIIa n AT III Fibrinogen Fibrin Stabilised fibrin  Low molecular weight heparins (LMWH) Heparin Pharmacodynamics Low molecular weight heparins (LMWH; fragments or synthetic heparin) have more consistent activity e.g. enoxaparin* LMWHs inactivate factor Xa (also via activation of antithrombin III) LMWH cannot inhibit thrombin (Factor IIa): LMWH is too short to form the ternary complex!!!!! Also Fondanparinux Synthetic form Also only inhibits factor Xa Blood clotting cascade Extrinsic Intrinsic pathway pathway Contact Tissue damage (e.g. with glass) VII VIIa XII XII a XIa X I IXa I X LMW X X Fondaparinux HATII a I XIII II IIa (Thrombi (Prothrombi n) n) XIIIa Fibrinogen Fibrin Stabilised fibrin WARFARIN nhibits Vit K epoxide reductase Vitamin K required for activation of coagulation factors Oral Medication Monitoring By PT/INR Blood clotting and warfarin Extrinsic Intrinsic pathway pathway Tissue damage Contact W VI VIIa XII XI I a I XIa X I W IXa I X W X Xa XIII W II (Prothrombi IIa (Thrombi n) n) XIIIa Fibrinogen Fibrin Stabilised fibrin Direct Oral Anticoagulants - DOAC Apixaban Edoxaban Rivaroxaban Inhibit Factor X Dabigatran Inhibits Thrombin Stable Angina Treatment Acute Offer a short-acting nitrate (sublingual GTN) for preventing and treating episodes of angina repeat the dose after 5 minutes if the pain has not gone call an emergency ambulance if the pain has not gone 5 minutes after taking a second dose Preventative Beta blocker/CCB Long lasting nitrate (isosorbide mononitrate), ivabradine, nicorandil, ranolazine Low dose aspirin/ statins if atherosclerosis Nitrates Mechanism NO – activates cGMP – relax smooth muscle asodilation – increases coronary blood flow and decreases preload Mechanism Angina Drug treatment for secondary prevention: taking into account the person's risk of bleeding and co- morbidities. aspirin (75 mg daily) statin. antihypertensive treatment. Reduce any modifiable risk factors For further information see the CKS topic on Lipid modification - CVD prevention and Hypertension - not diabetic  Fibrinolysis Breakdown of clot Streptokinase Alteplase https://healthjade.net/wp-content/uploads/2019/08/plasmin-function.jpg Invasive Methods Percutaneous Coronary Intervention (PCI) – coronary angioplasty Catheter to introduce stent Angioplasty Videos https://www.youtube.com/watch?v=I45kJJoCa6s (2:21 minute video) Additional videos 360 degree view of an angiogram – 6minutes https://www.bhf.org.uk/informationsupport/heart-matters- magazine/medical/watch-an-angiogram more detailed video https://www.bhf.org.uk/informationsupport/treatments/cor onary-angioplasty-and-stents Coronary Artery Bypass Grafting (CABG)