Coronary Artery Disease PDF

Coronary Artery Disease ILOs At the end of this session, the student will be able to: Understand the pathophysiology of stable and unstable coronary plaques. identify several mechanisms by which acute coronary syndromes can occur. Understand mechanisms by which the v...

Coronary Artery Disease ILOs At the end of this session, the student will be able to: Understand the pathophysiology of stable and unstable coronary plaques. identify several mechanisms by which acute coronary syndromes can occur. Understand mechanisms by which the various ischemic syndromes (stable and unstable angina, and acute MI) can be treated medically and with interventional therapies. Define the major risk factors for development of coronary artery disease. Outline the management plan of the different types of acute coronary syndromes. Explain the pathophysiology and presentation of chronic coronary syndromes. Summarize the treatment of chronic coronary syndromes. Risk factors for atherosclerotic coronary artery disease (CAD): Non-modifiable risk factors Modifiable risk factors Old age Hypertension Males more than females till the age of Dyslipidaemia 50 years Diabetes mellitus Genetic predisposition: family history Obesity of CAD Smoking Mental stress Sedentary life Pathophysiology of coronary artery disease: - Coronary artery atherosclerosis is the main pathology leading to myocardial ischemia. - The plaque is formed in the wall from haemodynamic sheer stress, deposition of lipids with certain biochemical changes. It has a cap, shoulders, smooth muscle cells and monocytes. - Stable atheromatous plaques cause chronic fixed narrowing of the coronary lumen and presents with stable angina. - Unstable plaques are liable to rupture and when this occurs it causes acute narrowing and presents with Acute Coronary Syndromes (ACS). Stable plaque Unstable plaque - Thick cap and shoulders. - Thin cap and ruptured - Small lipid core. shoulders. - Increased smooth muscle cells - Large lipid core. (SMCs). - Decreased number of SMCs. - Less monocytes. - Increased monocytes. Figure: Progression of atherosclerosis in CAD.  Ischemic Heart Disease (IHD) Acute Coronary Syndromes Chronic Coronary Syndromes (Chronic stable angina) ACUTE CORONARY SYNDROMES (ACS) Definitions: 1. Acute Coronary Syndromes (ACS): ACS is a clinical Presentation, in which the leading Symptom is prolonged angina (lasting more than 20 min), and the angina doesn’t relieve by SLG nitrates or rest. - Based on ECG, ACS comprises 2 subtypes: 1. Non-STE ACS (NSTEMI/UA): 2. STEMI: ECG: ECG: -Transient ST-segment elevation. -ST segment elevation mainly due -Persistent or transient ST-segment to complete occlusion of coronary depression. artery. -T-wave inversion. -Flattened T wave. - or may be normal ECG. 2. Definition of MI (Myocardial Infarction): Cardio myocyte necrosis in the clinical setting of acute myocardial ischemia. Elevate cardiac Cardiac cell death biomarkers Thus, to confirm ACS: 1. Symptom: Angina  2. ECG: Either STEMI or NSTEMI 3. Lab Tests: elevated cardiac biomarkers (Troponin & CK-MB) The following criteria are required to diagnose acute MI (AMI): - Rise and/or fall of cardiac biomarkers, preferably, high sensitivity cardiac troponin and at least one of the following: 1. Symptoms of ischemia 2. New or presumed new ST-segment changes or LBBB on 12-Lead ECG 3. Development of pathological Q waves 4. Imaging Evidence of new or presumed new loss of viable myocardium or regional wall motion abnormality e.g., by echocardiography 5. Intra-coronary thrombus detected by coronary angiography or autopsy. 3. Definition of angina (stable coronary artery disease = SCAD): Chest Pain: -Type: squeezing – dull - compressing -Site: precordium (Retrosternal) -Provoking factor: exertion -Relieving factors: Rest or SLG nitrates -Duration: 30 secs to few min. usually 3-5 min -Referral site: Neck – lower mandible – left or both shoulder – left or both arms & Axilla-Left or may be both forearms-left interscapular area. - Angina is stable when the provoking effort is constant and the duration for relief is constant.  4. Definition of unstable angina (UA): a) Angina crescendo = increase in the frequency & duration & severity (needs more than one SLG tablet for relief) b) Angina at rest c) Angina post ACS (Heart Attack): angina within the first month after ACS. d) Angina DE NOVO. ▪ Types of MI: - Type 1 MI: Atherosclerotic plaque -> rupture -> erosion ulceration or fissure -> platelet adhesion, aggregation & secretion -> thrombus -> occluded coronary artery -> myocardial infarction & ischemia. - Type 2 MI: Imbalance between myocardial oxygen demand and coronary blood supply. Causes of type 2 MI: a) Reduced myocardial perfusion: 1. Coronary artery spasm (Toxins or Drugs) 2. Coronary endothelial dysfunction 3. Coronary artery dissection 4. Sustained bradyarrhythmia (heart block) 5. Hypotension 6. Severe anaemia 7. Respiratory failure b) Increased myocardial Oxygen demand: 1. Sustained tachyarrhythmias 2. Severe hypertension ▪ Clinical examination: - The physical examination is usually not as sensitive or specific for ACS as history or diagnostic tests. - An unmarkable physical examination is not uncommon. - Perform a quick assessment of patients’ vital signs and perform a cardiac examination. - High risk features include: Systolic blood pressure less than 100 mm Hg or overt hypotension Elevated jugular venous pressure Presence of a third or fourth heart sound New or worsening apical systolic murmur due to papillary muscle dysfunction Rales or crackles Figure: Algorithm to rule-in and rule-out ACS.  Figure: Diagnosis and types of ACS ▪ Differential diagnosis of acute chest pain: ▪ Diagnosis of MI: Management of ACS ▪ Treatment of STEMI: - Aim of treatment is to restore coronary blood flow to the occluded coronary artery as soon as possible provided that the patient presented to 1st medical contact within the reperfusion window (12-24 hours of symptoms onset). - This is better achieved by Primary Percutaneous Coronary Intervention (PPCI) = Mechanical reperfusion (Balloon dilatation + Thrombus aspiration + Stenting), provided that it can be performed rapidly (less than 120 min from STEMI diagnosis). - If PPCI cannot be performed within the proper time ( 180/110). 5. Advanced liver disease. 6. Infective endocarditis. 7. Active peptic ulcer. 8. Prolonged traumatic resuscitation.  ▪ Adjunctive therapy in the management of STEMI: (Adjunctive to PPCI or fibrinolytic therapy): a) Dual antiplatelet therapy (DAPT) aspirin + P₂Y₁₂ inhibitor for 12 months: - Loading aspirin dose 150 – 300 mg orally & Loading dose of clopidogrel: 600 mg orally or loading dose of ticagrelor: 180 mg orally b) Parental anticoagulants: UFH = 70-100 IU/kg iv. Bolus Or Enoxaparin = 0.5 mg/ kg iv. Bolus Additional drug therapy: 1. Beta-blockers: in all ACS patients, especially if the left ventricle ejection fraction is less than 40%. 2. Lipid lowering therapy: high intensity statin therapy to achieve LDL- cholesterol level less than 55 mg/dl. 3. ACEI/ ARBs: in ACS patients with heart failure symptoms, with reduced EF ≤ 40%, with diabetes, or with hypertension. 4. MRAs: when EF ≤ 40% with heart failure or diabetes. Complications of STEMI: 1. Early complications: a. Sudden cardiac death b. Acute heart failure and pulmonary oedema c. Cardiogenic shock d. Mechanical complications i. Rupture of IVS => VSD ii. Ventricular rupture => tamponade (fatal) 1. pseudo-aneurysm iii. Ischemia to papillary muscle => acute MR. e. Arrhythmias i. -Ventricular tachycardia & fibrillation ii. -Brady arrhythmias and heart block f. Acute pericarditis 2. Late complications: 1. Recurrent ischemia (incomplete reperfusion) & re-infarction 2. Ventricular aneurysm 3. Mural thrombus & systemic embolism 4. Neurosis & anxiety ▪ Management of NSTEMI: - Aim: Rapid & effective relief of acute ischemia to prevent complications & to prevent deterioration to STEMI - Risk scoring is important to guide therapy (TIMI score & GRACE score) - It is important to identify those patients presenting with very high or high risk NSTEMI. Very high risk NSTEMI -> immediate invasive strategy (coronary angiography within 2hrs):  1. Haemodynamic instability and cardiogenic shock. 2. Recurrent or ongoing chest pain despite medical treatment 3. Life threatening arrhythmias 4. Mechanical complications: acute MR or VSD 5. Acute heart failure with refractory angina 6. Recurrent dynamic ST-T wave changes especially if intermittent ST elevation High risk NSTEMI->Early invasive strategy (coronary angiography within 24 hrs): 1. Rise or fall in cardiac troponin compatible with MI 2. Dynamic ST or T wave changes 3. GRACE score > 140 ▪ Adjunctive therapy: a) Dual antiplatelet therapy (DAPT) aspirin + P₂Y₁₂ inhibitor for 12 months: - Loading aspirin dose 150 – 300 mg orally & Loading dose of clopidogrel: 600 mg orally or loading dose of ticagrelor: 180 mg orally. b) Parental anticoagulants: UFH = 70-100 IU/kg iv. bolus Or Enoxaparin = 0.5 mg/ kg iv. Bolus. Additional drug therapy: 1. Beta-blockers. 2. Lipid lowering therapy. 3. ACEI/ ARBs. 4. MRAs. Chronic Coronary Syndromes (CCS) [Stable coronary artery disease (SCAD)] Definition: - Stable coronary artery disease is generally characterized by episodes of reversible myocardial demand/supply mismatch, related to ischaemia or hypoxia, which are usually inducible by exercise, emotion, or other stress and reproducible but, which may also be occurring spontaneously. Such episodes of ischaemia/hypoxia are commonly associated with transient chest discomfort (angina pectoris).  The most frequently encountered clinical scenarios in patients with suspected or established CCS are: (i) patients with suspected CAD and ‘stable’ anginal symptoms, and/or dyspnoea (ii) patients with new onset of heart failure (HF) or left ventricular (LV) dysfunction and suspected CAD (iii) asymptomatic and symptomatic patients with stabilized symptoms 1 year after initial diagnosis or revascularization (v) patients with angina and suspected vasospastic or microvascular disease (vi) asymptomatic subjects in whom CAD is detected at screening. Pathophysiology: The various clinical presentations of CCS are associated with different underlying mechanisms that mainly include: 1) plaque-related obstruction of epicardial arteries. 2) focal or diffuse spasm of normal or plaque-diseased arteries 3) microvascular dysfunction. 4) left ventricular dysfunction caused by prior acute myocardial necrosis and/or hibernation (ischemic cardiomyopathy). These mechanisms may act singly or in combination. Diagnosis and assessment: Symptoms and signs: - A careful history remains the cornerstone of the diagnosis of chest pain. - In the majority of cases, it is possible to make a confident diagnosis based on the history alone. - Angina pectoris: chest pain caused by myocardial ischemia is known as angina. 1. Location: The discomfort of angina is usually located in the chest, near the sternum, but may be felt anywhere from the epigastrium to the lower jaw or teeth, between the shoulder blades or in either arm to the wrist and fingers. 2. Character: The discomfort is often described as pressure, tightness or heaviness; sometimes strangling, constricting or burning. 3. Shortness of breath may accompany angina, and chest discomfort may also be accompanied by less-specific symptoms such as fatigue or faintness, nausea, burning, restlessness or a sense of impending doom.  Shortness of breath may be the sole symptom of SCAD. 4. Duration: The duration of the discomfort is brief (no more than 10 min in the majority of cases) but chest pain lasting for seconds is unlikely to be due to angina. 5. Relation to exacerbating and relieving factors: Symptoms classically appear or become more severe with increased levels of exertion—such as walking up an incline or against a breeze or in cold weather—and rapidly disappear within a few minutes when these causal factors abate. Exacerbations of symptoms after a heavy meal or after waking up in the morning are classical features of angina. Typical angina: Meets all three of the following characteristics: substernal chest discomfort of characteristic quality and duration. provoked by exertion or emotional stress. relieved by rest and/or nitrates within minutes. Atypical angina: Meets two of these characteristics. Non-anginal chest pain: Lacks or meets only one or none of the characteristics. Classification of angina severity according to the Canadian Cardiovascular Society: Class I: Ordinary activity does not cause angina such as walking and climbing stairs (chest pain on more than the usual daily efforts). Class II: Slight limitation of ordinary activity. Angina on walking or climbing stairs rapidly, walking or stair climbing after meals, or in cold, wind or under emotional stress. Class III: Marked limitation of ordinary physical activity. Angina on walking one to two blocks Class IV: Inability to carry on any physical activity without discomfort' – angina syndrome may be present at rest. Physical examination of a patient with (suspected) angina pectoris is important to assess the presence of anaemia, hypertension, valvular heart disease, hypertrophic obstructive cardiomyopathy or arrhythmias.  - It is also recommended that practitioners obtain the body mass index (BMI) and search for evidence of non-coronary vascular disease-which may be asymptomatic [includes palpation of peripheral pulses and auscultation of carotid and femoral arteries as well as assessment of the ankle brachial index (ABI)]—and other signs of comorbid conditions such as thyroid disease, renal disease or diabetes. - However, there are no specific signs in angina pectoris. During or immediately after an episode of myocardial ischemia, a third or fourth heart sound may be heard and mitral insufficiency may also be apparent during ischemia. Investigations: 1. Routine laboratory investigations: Complete blood picture, fasting lipid profile, fasting blood glucose level, HbA1c, renal and liver function. 2. Resting ECG for signs of ischemia. 3. Resting Echocardiography to evaluate resting wall motion, systolic and diastolic function, and differential diagnosis. 4. Stress testing for evaluation of ischemia: o Exercise stress ECG o Exercise and pharmacologic stress echocardiography o Myocardial perfusion scintigraphy (single photon emission computed tomography and positron emission tomography) o Stress cardiac magnetic resonance. 5. Assessment of the coronary anatomy: o Non-invasive using computed tomography (CT) coronary angiography or less commonly using magnetic resonance (MR) coronary angiography. o Invasive coronary angiography. Treatment: this includes A. Lifestyle modifications and control of risk factors B. Pharmacologic therapy C. Revascularization A. Life style modifications and control of risk factors:  Smoking cessation: quitting smoking is potentially the most effective of all preventive measures, being associated with a reduction in mortality of after MI. Diet: A healthy diet reduces CVD risk. Energy intake should be limited to the amount of energy needed to maintain (or obtain) a healthy weight—that is, a BMI of 25 kg/m2. Physical activity: Regular physical activity is associated with a decrease in CV morbidity and mortality in patients with established CAD. Aerobic exercise should be offered to patients with known CAD, usually as part of a structured cardiac rehabilitation program. Weight management: Both overweight and obesity are associated with an increased risk of death in CAD. Weight reduction in overweight and obese people is recommended. Lipid management: Dyslipidaemia should be managed according to lipid guidelines with pharmacological and lifestyle intervention. Patients with established CAD are regarded as being at very high risk for cardiovascular events and statin treatment should be considered, irrespective of low-density lipoprotein (LDL) cholesterol (LDL-C) levels. The goals of treatment are LDL-C below 1.4 mmol/L (55 mg/dL) or 50% LDL-C reduction. Management of hypertension. Diabetic control: Diabetes mellitus is a strong risk factor for CV complications, increases the risk of progression of coronary disease and should be managed carefully, with good control of glycated haemoglobin (HbA1c) to less than 7.0%. B. Pharmacological management of stable coronary artery disease patients: The aim is to reduce angina pain and to reduce further cardiovascular events. Anti-ischaemic drugs: 1. Nitrates. Nitrates offer coronary arteriolar and venous vasodilatation, which are the basis of symptomatic relief of effort angina, acting by their active component nitric oxide (NO) and by the reduction of preload. - Short-acting nitrates for acute effort angina. Sublingual nitro- glycerine is the standard initial therapy for effort angina. - Long-acting nitrates for long term angina pain prophylaxis.  1. B-blockers. b-blockers act directly on the heart to reduce heart rate, contractility, atrioventricular (AV) conduction and ectopic activity. Additionally, they may increase perfusion of ischaemic areas by prolonging the diastolic time. 2. Calcium channel blockers. Calcium antagonists (i.e. CCBs) act mainly by vasodilation and reduction of the peripheral vascular resistance. 3. Ivabradine. Ivabradine is a heart rate-lowering agent selectively inhibiting the sinus node I(f) pace making current, thereby decreasing the myocardial oxygen demand without effect on inotropism or BP. 4. Other drugs as Nicorandil, Ranolazine and Trimetazidine. Event prevention drugs: 1. Antiplatelet agents: Antiplatelet drugs decrease platelet aggregation and may prevent formation of coronary thrombus. - Low-dose aspirin - P2Y12 inhibitor (if allergy or contraindication to aspirin) 2. Lipid-lowering agents: Statins recommended for all patients with established SCAD. 3. Renin-angiotensin-aldosterone system blockers: ACE inhibitors for the treatment of patients with SCAD, especially with co-existing hypertension, LVEF ≤40%, diabetes or CKD unless contra-indicated. C. Revascularization: Revascularization is indicated in case of: failure of medical treatment, patients with high-risk findings in non-invasive tests and in cases of multivessel disease, left main stenosis and proximal LAD stenosis. Revascularization options include: 1. Percutaneous coronary intervention (PCI) 2. Coronary artery bypass graft (CABG) - Decision is made by heart team approach based on different clinical and anatomical risk scores.