CAD Lecture Notes PDF

CAD Prepared by: RANDA ALHARIZI Prof. Internal Medicine  Learning Outcomes By the end of this lesson, you should be able to: Define the natural history, pathophysiology, and presentations of coronary artery disease. Describe the clinical picture and...

CAD Prepared by: RANDA ALHARIZI Prof. Internal Medicine  Learning Outcomes By the end of this lesson, you should be able to: Define the natural history, pathophysiology, and presentations of coronary artery disease. Describe the clinical picture and Identify the indications, limitations, and risks of non-invasive and invasive investigations. Select investigations appropriately Outline life style and long-term risk factor management Outline drugs currently used in the treatment of stable angina Construct sensible D.D for a patient with acute coronary syndrome Select and use investigations appropriately to differentiate between STEMI, NSTEMI, and unstable angina Outline drugs currently used in the treatment of acute coronary syndromes.  Ischemic Heart Disease Definition Cardiac ischemia is due to imbalance between: Coronary flow = O2 supply Cardiac work = O2 needs Coronary circulation  LCA RCA Circumflex LAD RCA Posterior descending Right marginal branch  Epidemiology Most common cause of cardiovascular morbidity and mortality Atherosclerosis and thrombosis are the most important pathogenetic mechanisms Male:female ratio = 2:1 with all age groups included (Framingham study), 8:1 for age 70 Peak incidence of symptomatic IHD is age 50- 60 (men) and 60-70 (women)  Ischemic Heart Disease Risk Factors Fixed: Age, Male sex, Positive family history. Potentially changeable: Hyperlipidaemia, Cigarette smoking, Hypertension, Diabetes mellitus, Lack of exercise, Blood coagulation factors (high fibrinogen, factor VII), C-reactive protein, Homocysteinaemia, Obesity, excess alcohol intake.  Coronary Artery Atheroscler osis Pathogenesis of Atherosclerosis  Atherosclerosis Atherosclerosis is a process that can involve many of the body’s blood vessels with a variety of presentations. When it involves the coronary arteries it results in coronary artery disease The cerebral arteries; cerebrovascular disease (transient ischemic attack, stroke) The aorta; aortic aneurysms The ileo-femoral and popliteal arteries; peripheral vascular disease The mesenteric arteries; intestinal ischemia  CAD CAD can have the following clinical presentations: 1. Asymptomatic 2. Stable angina pectoris 3. Unstable angina (UA) pectoris 4. Myocardial Infarction (MI): either NSTEMI or STEMI 5. Sudden cardiac death  CHRONIC STABLE ANGINA Definition Symptom complex resulting from an imbalance between oxygen supply and demand in the myocardium  CAUSES 1- Factors that decrease myocardial oxygen supply Coronary blood flow to a region of the myocardium may be reduced by a mechanical obstruction that is due to: Atheroma (coronary atherosclerosis is the most important factor) Others: thrombosis, spasm, embolus, coronary ostial stenosis or coronary arteritis (e.g. in SLE). There can be a decrease in the flow of oxygenated blood to The myocardium that is due to: Anemia, carboxyhemoglobulinaemia or hypotension causing decreased coronary perfusion pressure. 2- Factors that increase myocardial oxygen demand Increased heart rate: hyperthyroidism, Increased contractility: hyperthyroidism or Increased wall stress: myocardial hypertrophy or aortic stenosis  Signs and Symptoms Typical: retrosternal chest pain, tightness or discomfort radiating to left (± right) shoulder/arm/neck/jaw, associated with diaphoresis, nausea, anxiety Predictably precipitated by the “3 Es”: exertion, emotion, eating Brief duration, lasting 5% , or those with markedly raised levels of single risk factors: cholesterol > 8 mmol/L, LDL cholesterol > 6 mmol/L, BP > 180/110 mmHg. All patients with diabetes. Close relatives of: patients with early-onset atherosclerotic cardiovascular disease Prevention may be by modifying life style or even drug therapy  Management Of Angina Pectoris I- General Measures 1- Change life style : Stop smoking Gradual exercise Weight reduction  2- Avoid : Exertion Emotions Eating heavy fatty meals Exposure to cold. 3-Treat 1- Hypertension 2-Diabetes mellitus 3-Hypercholesterolemia  MEDICAL TREATMENT Prognostic therapies Aspirin reduces the risk of coronary events in patients with coronary artery disease. All patients with angina, therefore, should take aspirin (75 mg daily is probably adequate) unless contraindicated. Lipid-lowering therapy should be used in patients with high total cholesterol or LDL-C, or low HDL-C despite a low fat diet.  Symptomatic treatment Glyceryl trinitrate (GTN) used sublingually, either as a tablet or as a spray, gives prompt relief. It can be used prior to performing activities that the patient knows will provoke angina. Patients require regular prophylactic therapy. The choice of drugs is between beta-blockers, nitrates and calcium-channel blockers or combination therapy. Treatment needs to be tailored to the individual patient. Patients not controlled adequately on medical therapy should be considered for revascularization Beneficial effects of nitrate in angina - Decreased O2 requirement due to decreased B.P., decreased ventricular volume and ejection time. - Increased O2 supply by dilating epicardial coronary vessels and increased collateral flow and decreased left ventricular diastolic pressure. O2 supply O2 O2needs needs O2 supply Precautions: - 8-10 Hours nitrate-free period or alternate every 2 weeks to avoid tolerance with long acting nitrate. - Never Stop nitrate therapy Suddenly → Rebound ischemia & infarction. - Not combined with Sildenafil (Viagra) → Severe Hypotension → May be Fatal  Beta blockers: Decrease cardiac work and oxygen consumption Calcium channel blockers: Vasodilator  Other Anti- Anginal Drugs Nicorandil - Oral V.D. →  Preload & Afterload: a- Nitrate-like → Release NO = Arterio-venodilator. b- Opens ATP-dependent K+-Channel. - V.D. of Normal Large Epicardial coronaries. - Useful in Angina & Heart failure. - No tolerance. - Headache.  Other Anti-Anginal Drugs Ranolazine is a novel agent that interacts with sodium channels and can improve exercise tolerance and reduce the frequency of angina attacks in patients with ischaemic heart disease. It causes QT interval prolongation Reserved for patients who do not respond to other antianginal drugs. Ivabradine is a selective and specific inhibitor of the cardiac pacemaker For symptomatic treatment of chronic stable angina pectoris in patients with normal sinus rhythm who have a contraindication or intolerance to beta-blockers.  ACE Inhibitors ACEI, NOT used to treat symptomatic angina Benefit in all patients at high risk for CV disease (concomitant DM, renal dysfunction, or LV systolic dysfunction)  IV- Anti-Platelet Drugs 1- Aspirin in SD: (75–150 mg) →  Platelet TXA-2. Also treats Nitrate-induced headache 2- ADP-Receptors Blockers: Ticlopidine & Clopidogrel. 3- GP IIb/IIIa-Receptors Blockers: Abciximab & Tirofiban Percutaneous coronary intervention Percutaneous coronary intervention (PCI) is the process of dilating a coronary artery stenosis using an inflatable balloon and stent insertion introduced into the arterial circulation via the femoral, radial or brachial artery PCI PCI PCI & STENT Coronary artery bypass grafting With coronary artery bypass grafting (CABG) autologous veins or arteries are anastamosed to the ascending aorta and to the native coronary arteries distal to the area of stenosis CABG  Coronary Artery Bypass Grafting Main indications for CABG: Three-vessel disease with >70% stenosis in each vessel. Left main coronary disease with >50% stenosis. Left ventricular dysfunction.  Variant (Prinzmetal, Vaso-spastic) Angina Myocardial ischemia Due to reversible coronary vasospasm (Supersensitive coronary) with or without atherosclerosis Uncommonly associated with infarction or LV dysfunction Typically occurs between midnight and 8 AM, unrelated to exercise, relieved by nitrates Typically ST elevation on ECG Diagnosed by provocative testing with ergot vasoconstrictors (rarely done) Treatment by Coronary V.D. nitrates and CCBs Refractory Angina Refers to patients with severe coronary disease in whom revascularization is not possible and angina is not controlled by medical therapy. Microvascular Angina Patients have exercise-induced angina but normal or unobstructed coronary arteries (on coronary angiography, CTCA). Intracoronary acetylcholine may cause coronary spasm. Whilst they have a good prognosis, they are often highly symptomatic and can be difficult to treat. In women with this syndrome, the myocardium shows an abnormal metabolic response to stress, consistent with the suggestion that the myocardial ischemia results from abnormal dilator responses of the coronary microvasculature to stress. ACUTE CORONARY SYNDROME Acute Coronary syndrome - Emergency case  ACS includes the spectrum of UA [unstable angina], NSTEMI [non S-T segment elevated myocardial infarction] and STEMI [S-T segment elevated myocardial infarction]. This distinction aids in providing the appropriate therapeutic intervention Relationship between the state of coronary artery vessel wall and clinical syndrome Clinical picture Chest pain lasting more than 20minutes Pain does not respond to sublingual glyceryl trinitrate Pain may radiate to the left arm, neck or jaw. However, in elderly or diabetic ones, the symptoms may be atypical and include dyspnea, fatigue, pre- syncope or syncope. The patient may be pale and clammy, with marked sweating. Pulse may be thready with significant hypotension, bradycardia or tachycardia. MYOCARDIAL INFARCTION MI is defined by evidence of myocardial necrosis. It is diagnosed by a rise of serum markers PLUS any one of: Symptoms of ischemia (chest/upper extremity/mandibular/epigastric discomfort; dyspnea) ECG changes (ST-T changes, new BBB or pathological Q waves) Imaging evidence (myocardial loss of viability, wall motion abnormality or intracoronary thrombus) MYOCARDIAL INFARCTION NSTEMI meets criteria for myocardial infarction without ST elevation or BBB STEMI meets criteria for myocardial infarction characterized by ST elevation or new BBB ECG showing S-T segment elevated myocardial infarction ECG showing depressed S-T segment (ischemia)  UNSTABLE UNGINA UA is clinically defined by any of the following ❑Accelerating pattern of pain: increased frequency, increased duration, decreased threshold of exertion, decreased response to treatment ❑Angina at rest ❑New-onset angina ❑Angina post-MI or post-procedure (e.g. percutaneous coronary intervention [PCI], coronary artery bypass grafting [CABG])  Investigations ECG CXR Labs Serum cardiac biomarkers for myocardial damage as Troponin I & T, CK-MB, myoglobin (repeat 8 h later) CBC, INR/PTT, electrolytes and magnesium, creatinine, urea, glucose, serum lipids  Cardiac markers Troponin T and I: more specific, If the initial troponin assay is negative, then it should be repeated 4–12 h later. The troponin assay has prognostic information: that is, a high serum troponin level has an increased mortality risk in ACS, and defines which patients may benefit from aggressive medical therapy and early coronary revascularization.  CK-MB level was the standard marker for myocyte death used in ACS. However, the presence of low levels of CK-MB in the serum of normal individuals and in patients with significant skeletal muscle damage has limited its accuracy. It can, however, be used to determine re- infarction, as levels drop back to normal after 36– 72 h. Myoglobin becomes elevated very early in MI but the test has poor specificity for ACS, as myoglobin is present in skeletal muscle. Localization of STEM Infarction  MANAGEMENT OF ACUTE CORONARY SYNDROMES 1. General measures ABCs: assess and correct hemodynamic status first Bed rest, cardiac monitoring, oxygen Nitroglycerin SL followed by IV Morphine IV  Within the first 10 minutes of presentation, carry out the following initial steps (mnemonic: ABC, ECG, MONA, LABs) LAB ECG s  MNEMONI C MONA Morphine: Administration of 2- to 4 mg IV morphine reduces cardiac workload by decreasing sympathetic stimulation as a result of pain and anxiety. Oxygen (O2): Maintain oxygen saturation (SaO2) >94% with supplemental O2. (does not help non-hypoxic patients) Nitroglycerin: Administer three doses of 0.4 mg sublingual nitroglycerin every 5 minutes. Nitrates are contraindicated if the patient has taken a 5-PDE inhibitor such as Viagra or Cialis in the last 24 to 36 hours because the combination can cause severe hypotension. Aspirin: Give all patients 160 to 325 mg aspirin (antiplatelet therapy) unless it is contraindicated. Aspirin is the only MONA therapy that improves mortality. Management of UA and NSTEMI  Antiplatelet therapy ACS patients should be treated with dual antiplatelet agents: aspirin 300mg loading dose then 75-100mg daily and an ADP-receptor antagonist: clopidogrel 300– 600mg loading then 75mg daily or prasugrel 60mg loading then 10mg daily or ticagrelor 180mg loading then 90mg twice daily  Antithrombin drugs An antithrombin should be added to dual antiplatelets in patients with ACS. Unfractionated heparin (UFH) requires frequent monitoring; the low-molecular-weight heparin enoxaparin appears to be superior Bivalirudin, a direct thrombin inhibitor, appeared as effective as heparin plus GPIIb/IIIa inhibitors in reducing ischaemic events in patients undergoing diagnostic angiography or percutaneous intervention, but with less bleeding.  Glycoprotein (GP) IIb/IIIa receptor antagonists Receptor antagonists (abciximab, eptifibatide, tirofiban) are powerful inhibitors of platelet aggregation. However, their use in ACS patients should be restricted to patients with heavy thrombus burden identified during coronary angiography and for complications during PCI (e.g. distal embolization).  Anti-ischemia agents beta-blockers In patients with no contraindications (asthma, AV block, acute pulmonary edema) lower the heart rate and blood pressure, reducing myocardial oxygen consumption. The dose can be titrated to produce a resting heart rate of 50–60b.p.m. nitrates either sublingually or intravenously. They effectively reduce preload and produce coronary vasodilation.  Plaque stabilization/remodelling HMG-CoA reductase inhibitor drugs (statins) and ACE inhibitors are routinely administered to patients with ACS. These agents may produce plaque stabilization, improve vascular and myocardial remodelling, and reduce future cardiovascular events. Starting the drugs while the patient is still in hospital increases the likelihood of these individuals receiving secondary drug therapy.  Coronary angiography and intervention More than 90% of patients improve with the above medical regimen within 1 to 2 days. The choice of invasive management (early catheterization/revascularization within 48 hours) versus conservative management (catheterization/revascularization only if medical therapy fails) is controversial. Very high-risk patients require urgent coronary angiography (140) require coronary angiography within 24h. Intermediate-risk patients with diabetes mellitus, renal impairment (estimated glomerular filtration rate < 60), LVEF below 40% or congestive cardiac failure, early post infarction angina, previous PCI or CABG, or a GRACE score of over 109 but less than 140 require coronary angiography within 72 h Low-risk patients can be managed initially with medical therapy but an invasive strategy with cardiac catheterization is preferred in most patients  TIMI Score – The Thrombolysis in Myocardial Infarction (TIMI) risk score can also be used to guide the decision on conservative versus more aggressive treatment in acute coronary syndrome (NSTEMI/UA)  The TIMI risk score Low risk score = 0–2, Intermediate risk = 3–4, High risk = 5–7.  TIMI UA/NSTEMI Risk Score Predicts risk of death, new/recurrent MI, need for urgent revascularization within 14 days  How would you manage a patient based on his TIMI score? Intermediate- to high-risk patients should undergo coronary angiography within 48 hours. Perform PCI or CABG on the basis of coronary angiography findings (indications for CABG over PCI are the same as those in patients with stable angina). Before the patient is discharged, perform echocardiogram, submaximal stress test, and medications (ABC N' ACE, STAT). With low-risk TIMI, angiography not necessary; obtain stress test before discharge. Do not administer thrombolytics for UA or NSTEMI. This is because the thrombi are nonocclusive and platelet-rich. Such thrombi do not respond to thrombolytics like the fibrin-rich thrombi in STEMI.  Treatment After the acute treatment Continue aspirin (or other antiplatelet therapy), β-blockers (atenolol or metoprolol), and nitrates Reduce risk factors – Smoking cessation, weight loss – Treat diabetes, HTN – Treat hyperlipidemia—patients with any form of CAD (stable angina, UA, NSTEMI, STEMI) should be started on an HMG-CoA reductase inhibitor regardless of LDL level. Clinical trials of statins have shown the efficacy of such therapy for secondary prevention in CAD Patients who receive a bare metal stent must take Ticagrelor daily for 1 month, and those who received a drug-eluting stent must take Ticagrelor for 1 year Management of STEMI  Management of STEMI Initial assessment involves rapid triage for chest pain (note that time is muscle) and referral for reperfusion therapy (primary PCI or thrombolysis). Initial medical therapy includes oxygen (if saturations are 4 mEq/L because hypokalemic patients have an increased risk of ventricular fibrillation. Maintain Mg+2 >2 mEq/L because serum potassium will not rise with concurrent hypomagnesemia. 6. Low–molecular-weight heparin (LMWH) is superior to unfractionated heparin. Goal is to prevent progression or development of a clot Should be continued for at least 2 days Enoxaparin is the drug of choice based on clinical trials  Methods of Revascularization Percutaneous Coronary Intervention “Gold Standard” This is the preferred treatment for STEMI as long as it can be performed expeditiously (door to balloon time less than 90 minutes) and by skilled personnel. Also preferred in patients with contraindications for thrombolytic therapy; no risk of intracranial hemorrhage. Trials showed that PCI reduces mortality more than t-PA.  Methods of Revascularization Thrombolytic Therapy (“door to needle time” 7 g of omega 3 fatty acids/week from oily fish Patients should be physically active for 20–30 min/day. Patients should stop smoking. Maintain a healthy weight. Patients with hypertension should be treated to < 140/90 or < 130/80 if chronic kidney disease or DM Patients with diabetes should be treated to maintain HbA1c < 7%.  Rehabilitation Cardiac rehabilitation is a physician-supervised regimen of exercise and risk factor reduction after MI. Shown to reduce symptoms and prolong survival. What medications should this patient take after STEMI? There are several discharge medications suitable after STEMI (mnemonic: “ABC N' ACE, STAT!”): ABC: Aspirin, β-1 Blockers, and Clopidogrel reduce mortality after STEMI. Nitrates are used for symptom relief but do not reduce mortality. ACE inhibitors reduce mortality after STEMI. The mechanism is decreased LV remodeling, which lowers risk of subsequent CHF and recurrent MI. Initiate ACE inhibitors within 24 hours as long as they are not contraindicated. If the patient cannot tolerate an ACE inhibitor, substitute with an ARB (specifically valsartan or candesartan). STATins.  Post-MI drug therapy and assessment (CONT) Uncomplicated patients with no angina during the hospital stay should have a low-level exercise test prior to discharge followed by a formal ETT 6 weeks later. A positive test usually suggests diagnostic/therapeutic coronary angiography/stenting. Alternatively, nuclear scintigraphy or dobutamine stress echocardiography can be used at 5 days to determine the amount of viable myocardium and the extent of myocardial ischaemia. Echocardiography should be performed to guide therapy and to determine baseline ejection fraction. Complications of MI  Complications of MI Arrhythmia [First 48 h] Shock/CHF [48 h] 1. Tachycardia Post-Infarct Angina 2. Bradycardia [Anytime] Myocardial Rupture [1- Recurrent MI [Anytime] 7 d] Thromboembolism [7- 1. LV free wall 10 d, up to 6 mo] 2. Papillary muscle (MR) Pericarditis [1-7 d] 3. Ventricular septum Dressler’s syndrome [2- (VSD) 8 weeks]  Prognosis following STEMI 5-15% of hospitalized patients will die Risk factors: infarct size/severity, age, co-morbid conditions, development of heart failure or hypotension Post-discharge mortality rates 6-8% within first year, half of these within first 3 months 4% per year following first year Risk factors: LV dysfunction, residual myocardial ischemia, ventricular arrhythmias, history of prior MI Summary Early Invasive Conservative Management of a patient with chest pain  References Kumar & Clark’s Clinical Medicine 10th edition page 1079-1091  Quiz Which of the following is the usual findings during clinical examination of patients with stable angina? Usually no abnormal findings Usually there is mitral valve regurge Gallop over the apex of the heart Basal lung crepitation  Quiz Which of the following drugs has mortality benefit effects in treatment of acute coronary syndrome? Nitrates Calcium channel blockers Beta blockers Frusemide