Acute Coronary Syndrome, Arrhythmia, and Cardiac Arrest Lecture Notes PDF

Clinical Pharmacy and Therapeutics Acute Coronary PHCP 311 Syndrome Our Lady of Fatima University College of Pharmacy Learning Outcomes At the end of the discussion, the student must be able: To explain the pathop...

Clinical Pharmacy and Therapeutics Acute Coronary PHCP 311 Syndrome Our Lady of Fatima University College of Pharmacy Learning Outcomes At the end of the discussion, the student must be able: To explain the pathophysiology of the Acute Coronary syndrome To identify the factors that may induce and potentiate the disease To discuss the clinical presentation as well the diagnosis and laboratory evaluation. To evaluate the therapeutic outcome. Acute coronary syndrome (ACS) includes all syndromes compatible with acute myocardial ischemia resulting from imbalance between myocardial oxygen demand and supply. ACS is classified according to electrocardiographic (ECG) changes into: A. ST segment- elevation myocardial infarction (STEMI) B. non–ST-segment-elevation ACS (NSTE-ACS), which includes: non–ST-segment-elevation MI (NSTEMI) unstable angina (UA). Pathophysiology Endothelial dysfunction, inflammation, and formation of fatty streaks contribute to development of atherosclerotic coronary artery plaques. With rupture of an atherosclerotic plaque, exposure of collagen and tissue factor induces platelet adhesion and activation, promoting release of adenosine diphosphate (ADP) and thromboxane A2 from platelets, leading to vasoconstriction and platelet activation. A change in the conformation of the glycoprotein IIb/IIIa surface receptors of platelets occurs that cross-links platelets to each other through fibrinogen bridges. Simultaneously, activation of the extrinsic coagulation cascade occurs as a result of exposure of blood to the thrombogenic lipid core and endothelium, which are rich in tissue factor. This leads to formation of a fibrin clot composed of fibrin strands, cross-linked platelets, and trapped red blood cells. Subtypes of MI are based on etiology: Type 1: Rupture, fissure, or erosion of an atherosclerotic plaque (90% of cases); Type 2: Reduced myocardial oxygen supply or increased demand in the absence of a coronary artery process; Type 3: MI resulting in death without the possibility of measuring biomarkers; Type 4: MI associated with percutaneous coronary intervention (PCI; Type 4a) or stent thrombosis (Type 4b); Type 5: MI associated with coronary artery bypass graft (CABG) surgery Clinical Presentation Ventricular remodeling after MI is characterized by left ventricular (LV) dilation and reduced pumping function, leading to heart failure (HF). Complications of MI include cardiogenic shock, HF, valvular dysfunction, arrhythmias, pericarditis, stroke secondary to LV thrombus embolization, venous thromboembolism, LV free-wall or septal rupture, aneurysm formation, and ventricular and atrial tachyarrhythmias. The predominant symptom is midline anterior chest pain (usually at rest), severe new-onset angina, or increasing angina that lasts at least 20 minutes. Discomfort may radiate to the shoulder, down the left arm, to the back, or to the jaw. Accompanying symptoms may include nausea, vomiting, diaphoresis, and shortness of breath. No specific features indicate ACS on physical examination. However, patients with ACS may present with signs of acute decompensated HF or arrhythmias. Obtain 12-lead ECG within 10 minutes of presentation ST-segment depression, and T-wave inversion Appearance of a new left bundle-branch block with chest discomfort is highly specific for acute MI. Diagnosis of MI is confirmed with detection of rise and/or fall of cardiac biomarkers (mainly troponin T or I) with at least one value above the 99th percentile of the upper reference limit and at least one of the following: Symptoms of ischemia Sew significant ST-segment–T-wave changes or new left bundle-branch block; Pathological Q waves; Imaging evidence of new loss of viable myocardium or new regional wall motion abnormality. Typically, a blood sample is obtained once in the emergency department, then 3 to 6 hours after symptom onset. Goals of Treatment: Short term goal: Early restoration of blood flow to the infarct-related artery to prevent infarct expansion (in the case of MI) or prevent complete occlusion and MI (in UA), Prevention of death and other complications, Prevention of coronary artery reocclusion, Relief of ischemic chest discomfort, Resolution of ST-segment and T-wave changes on ECG. Long term goal: control of cardiovascular (CV) risk factors, prevention of additional CV events, and improvement in quality of life Evaluation of the acute coronary syndrome patient Normal Pattern Patients with STEMI are at high risk of death, so initiate immediate efforts to reestablish coronary perfusion and adjunctive pharmacotherapy. For patients with STEMI presenting within 12 hours of symptom onset, early reperfusion with primary PCI of the infarct artery within 90 minutes of first medical contact is the reperfusion treatment of choice. For patients with NSTE-ACS, practice guidelines recommend an early (within 24 hours) invasive strategy with left heart catheterization, coronary angiography, and revascularization with either PCI or CABG surgery as early treatment for high-risk patients; such an approach may also be considered for patients not at high risk. ST Segment Elevation A Options after coronary angiography also include medical management alone or CABG surgery. B Clopidogrel preferred P2Y12 inhibitor when fibrinolytic therapy is utilized. No loading dose recommended if age older than 75 years. C Given for up to 48 hours or until revascularization. D Given for the duration of hospitalization, up to 8 days or until revascularization. E If pretreated with UFH, stop UFH infusion for 30 minutes prior to administration of bivalirudin (bolus plus infusion). F In patients with STEMI receiving a fibrinolytic or who do not receive reperfusion therapy, administer clopidogrel for at least 14 days and ideally up to 1 year. (ACE, angiotensin-converting enzyme; ARB, angiotensin receptor blocker; ASA, aspirin; CI, contraindication; FMC, first medical contact; GPI, glycoprotein IIb/IIIa inhibitor; IV, intravenous; MI, myocardial infarction; NTG, nitroglycerin; PCI, percutaneous coronary intervention; SC, subcutaneous; SL, sublingual; UFH, unfractionated heparin.) All patients with STEMI and without contraindications should receive within the first day of hospitalization and preferably in the emergency department: ☐ A. Intranasal oxygen (if oxygen saturation is low), ☐ B. Sublingual (SL) nitroglycerin (NTG), ☐ C. Aspirin ☐ D. P2Y12 platelet inhibitor ☐ E. anticoagulation with bivalirudin, unfractionated heparin (UFH), enoxaparin, or fondaparinux (depending on reperfusion strategy). Fibrinolytic therapy Indicated in patients with STEMI who present within 12 hours of the onset of chest discomfort to a hospital not capable of primary PCI and have at least a 1-mm STE in two or more contiguous ECG leads, have no absolute contraindications to fibrinolytic therapy and cannot be transferred and undergo primary PCI within 120 minutes of medical contact. Fibrinolytic use between 12 and 24 hours after symptom onset should be limited to patients with ongoing ischemia. Preference: Fibrin specific > Streptokinase Contraindication for Fibrinolytics Any prior intracranial hemorrhage, known structural cerebrovascular lesion (eg, AV malformation), known intracranial neoplasm, ischemic stroke within 3 months, active bleeding (excluding menses), and significant closed head or facial trauma within 3 months. Primary PCI is preferred in these situations. Treat eligible patients as soon as possible, but preferably within 30 minutes from the time they present to the emergency department, with one of the following regimens: Alteplase Reteplase Tenecteplase Streptokinase Intracranial Hemorrhage Most serious ADR of fibrinolytics Fibrin specific > streptokinase Systemic bleeding Streptokinase > Fibrin specific Aspirin Administer aspirin to all patients without contraindications within 24 hours before or after hospital arrival. It provides additional mortality benefit in patients receiving fibrinolytic therapy. Give non–enteric-coated aspirin (which may be chewed for more rapid effect) 162 to 325 mg regardless of the reperfusion strategy being considered PCI not previously taking aspirin should receive 325-mg non–enteric-coated aspirin Maintenance dose: 75- 165 mg daily, if given with ADP inhibitor, 81 mg (low dose) is preferred to avoid bleeding Discontinue NSAIDs and COX inhibitors at the time of STEMI Increase risk of death, reinfarction and heart failure ADR: dyspepsia, nausea, bleeding Platelet P2Y12 Inhibitors ( ADP inhibitors) Prevents binding of ADP to the receptor and subsequent expression of platelet GP IIb/IIIa receptors, reducing platelet aggregation. Oral: Clopidogrel, Prasugrel, Ticagrelor IV: Cangrelor ☐ In adults younger than 75 years receiving fibrinolytics, the first dose of clopidogrel can be a 300-mg loading dose ADP inhibitor + Aspirin: recommended for all STEMI patients ARD: Clopidogrel: hypersensitivity, Thrombocytopenic purpura Ticagrelor: Nausea, diarrhea, dyspnea (19%), brady arrhythmias Glycoprotein IIb/IIIa Receptor Inhibitors GPIs block the final common pathway of platelet aggregation, namely, cross-linking of platelets by fibrinogen bridges between the GP IIb and IIIa receptors on the platelet surface Do not administer GPIs to patients with STEMI who will not be undergoing PCI. o Abciximab: 0.25-mg/kg IV bolus given 10 to 60 minutes before the start of PCI, followed by 0.125 mcg/kg/min (maximum 10 mcg/min) for 12 hours. o Eptifibatide: 180-mcg/kg IV bolus, repeated in 10 minutes, followed by infusion of 2 mcg/kg/min for 18 to 24 hours after PCI. o Tirofiban: 25-mcg/kg IV bolus, then 0.15 mcg/kg/min up to 18 to 24 hours after PCI. Contraindications: Px with history of hemorrhagic stroke or recent ischemic stroke. Px with CKD o Reduce dose of Epfibatide and tirfiban ADR: immune-mediated thrombocytopenia Anticoagulants Either UFH or bivalirudin is preferred for patients undergoing primary PCI, whereas for fibrinolysis, either UFH, enoxaparin, or fondaparinux may be used. UFH: initial dose for primary PCI is 50 to 70 units/kg IV bolus if a GPI is planned and 70 to 100 units IV bolus if no GPI is planned; Enoxaparin: 1 mg/kg subcutaneous (SC) every 12 hours (creatinine clearance [Clcr] ≥30 mL/min) or once every 24 hours if impaired renal function (Clcr 15–29 mL/min). Bivalirudin dose for PCI in STEMI is 0.75 mg/kg IV bolus, followed by 1.75 mg/kg/h infusion. Discontinue at the end of PCI Fondaparinux dose is 2.5 mg IV bolus followed by 2.5 mg SC once daily starting on hospital day 2. For patients undergoing PCI, discontinue anticoagulation immediately after the procedure. β-Adrenergic Blocker Blockade of β1 receptors in the myocardium o reduces heart rate, myocardial contractility, and BP, thereby decreasing myocardial oxygen demand o Reduced heart rate increases diastolic time, thus improving ventricular filling and coronary artery perfusion. o Reduce risk for recurrent ischemia, infarct size, reinfarction, and ventricular arrhythmias in the hours and days after an MI Limited to patients who present with hypertension or signs of myocardial ischemia and do not have signs or symptoms of acute HF. o Risk of Cardiogenic shock Patients already taking β-blockers can continue taking them. Metoprolol, Propranolol, Atenolol o Continue β-blockers for at least 3 years in patients with normal LV function and indefinitely in patients with LV systolic dysfunction and LVEF of 40% or less. o ADR: hypotension, acute HF, bradycardia, and heart block. Statins Administer a high-intensity statin (atorvastatin 80 mg or rosuvastatin 40 mg) to all patients prior to PCI (regardless of prior lipid-lowering therapy) to reduce the frequency of periprocedural MI (Type IVa MI) following PCI Nitrates NTG causes venodilation, which lowers preload and myocardial oxygen demand. Arterial vasodilation may lower BP, thereby reducing myocardial oxygen demand. Arterial dilation also relieves coronary artery vasospasm and improves myocardial blood flow and oxygenation Immediately upon presentation, administer one SL NTG tablet (0.4 mg) every 5 minutes for up to three doses to relieve chest pain and myocardial ischemia. Intravenous NTG is indicated for patients with an ACS who do not have a contraindication and who have persistent ischemic discomfort, HF, or uncontrolled high BP. ☐ Oral nitrates play a limited role in ACS ADR: tachycardia, flushing, headache, and hypotension C/I: Patients taking PD5-I o sildenafil or vardenafil within the prior 24 hours o tadalafil within the prior 48 hours Calcium Channel Blockers After STEMI, calcium channel blockers (CCBs) are used for relief of ischemic symptoms in patients who have contraindications to β-blockers. Non dihydropyridine ( diltiazem, verapamil) > dihydropyridine Except: LV systolic dysfunction, bradycardia, or heart block. ☐Give Amlodipine or Felodipine ☐Avoid Nifedipine ☐causes reflex sympathetic activation tachycardia, and worsened myocardial ischemia. Important Precautions Early pharmacotherapy for NSTE-ACS is similar to that for STEMI. In absence of contraindications, treat all patients in the emergency department with intranasal oxygen (if oxygen saturation is low), SL NTG, aspirin, and an anticoagulant (UFH, enoxaparin, fondaparinux, or bivalirudin). High-risk patients should proceed to early angiography and may receive a GPI (optional with either UFH or enoxaparin but should be avoided with bivalirudin). Administer a P2Y12 inhibitor to all patients; choice and timing depend on the interventional approach selected. Give IV β-blockers and IV NTG to select patients. Initiate oral β-blockers within the first 24 hours in patients without cardiogenic shock. Give morphine to patients with refractory angina Never administer fibrinolytic therapy in NSTE-ACS. Aspirin Aspirin reduces risk of death or MI by approximately 50% compared with no antiplatelet therapy in patients with NSTE-ACS. Anticoagulants Early invasive approach with early coronary angiography and PCI, administer UFH, enoxaparin, fondaparinux, or bivalirudin. If Initial ischemia-guided strategy: (no coronary angiography or revascularization), enoxaparin, UFH, or low-dose fondaparinux is recommended Continue therapy for at least 48 hours for UFH, until the patient is discharged from the hospital P2Y12 Inhibitors A P2Y12 receptor inhibitor (plus aspirin) is recommended for most patients with NSTE-ACS. They are the preferred antiplatelet agents because of efficacy and ease of use, resulting in decreased use of IV antiplatelet agents such as GPIs invasive management strategy: Ticagrelor or clopidogrel prehospital or in ED Following PCI, continue dual oral antiplatelet therapy for at least 12 months. initial conservative strategy: clopidogrel or ticagrelor can be administered in addition to aspirin. ☐ Continue dual antiplatelet therapy for at least 12 months. Nitrates Administer SL NTG followed by IV NTG to patients with NSTE-ACS and ongoing ischemia, HF, or uncontrolled high BP. Continue IV NTG for approximately 24 hours after ischemia relief. β-Blockers In the absence of contraindications, administer oral β-blockers to patients with NSTE-ACS within 24 hours of hospital admission. Continue β-blockers indefinitely in patients with LVEF of 40% or less and for at least 3 years in patients with normal LV function. Calcium Channel Blockers limited to patients with certain contraindications to β-blockers and those with continued ischemia despite β-blocker and nitrate therapy. Diltiazem and verapamil are preferred unless the patient has LV dysfunction, Alternative: Amlodipine or Felodipine C/I: Nifedipine SECONDARY PREVENTION FOLLOWING MI 1. treat and control modifiable risk factors such as hypertension, dyslipidemia, obesity, smoking, and diabetes mellitus (DM). 2. indefinite treatment with: A. Aspirin 81 mg/day (or clopidogrel if aspirin contraindications) B. ACE inhibitor or ARBs C. High-intensity statin D. β-blocker for at least 3 years in patients with normal LV function and indefinitely in patients with LVEF of 40% or less; o Alternative: CCBs E. P2Y12 inhibitor for at least 1 year in most patients with STEMI or NSTEACS. F. Short-acting SL NTG or lingual NTG spray, PRN for anginal relief RELATED LINK/VIDEO https://www.youtu be.com/watch?v= hIvmjPafaFg&feat ure=youtu.be  REFERENCES ∙ Boyette LC, Manna B. Physiology, Myocardial Oxygen Demand. [Updated 2019 Apr 3]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK499897/ ∙ Kumar, A., & Cannon, C. P. (2009). Acute coronary syndromes: diagnosis and management, part I. Mayo Clinic proceedings, 84(10), 917–938. https://doi.org/10.1016/S0025-6196(11)60509-0 ∙ Walker, Roger &th Whittlesea, Cate. (2012). Clinical Pharmacy & Therapeutics. 5 ed. Elsevier Ltd.  Clinical Pharmacy and Therapeutics Our Lady of Fatima Arrhythmia University College of Pharmacy PHCP311 Learning Outcomes At the end of the discussion, the student must be able: To explain the pathophysiology of the Arrhythmia To identify the factors that may induce and potentiate the disease To discuss the clinical presentation as well the diagnosis and laboratory evaluation. To evaluate the therapeutic outcome. Arrhythmia Arrhythmia is loss of cardiac rhythm, especially irregularity of heartbeat. Ventricular arrhythmias: occur in the lower chambers of the heart, called the ventricles. Supraventricular arrhythmias: occur in the area above the ventricles, usually in the upper chambers of the heart, called the atria. The irregular beats can either be too slow (bradycardia) or too fast (tachycardia). SUPRAVENTRICULAR ARRHYTHMIA Supraventricular tachycardias requiring drug treatment A. Atrial fibrillation (AF) B. Atrial flutter C. Paroxysmal supraventricular tachycardia (PSVT). Arrhythmias that usually do not require drug therapy: A. Premature atrial complexes, B. Sinus arrhythmia C. Sinus tachycardia Atrial Fibrillation AF has extremely rapid (400–600 atrial beats/min) and disorganized atrial activation. (Narrow QRS, Irregular rhythm) There is loss of atrial contraction (atrial kick), and supraventricular impulses penetrate the atrioventricular (AV) conduction system to variable degrees, resulting in irregular ventricular activation and irregularly irregular pulse (120–180 beats/min). Atrial fibrillation: Irregularly irregular ventricular rate without visible P waves Atrial Flutter Atrial flutter has rapid (270–330 atrial beats/min) but regular atrial activation. Narrow QRS, Regular Rhythm Ventricular response usually has a regular pattern and a pulse of 300 beats/min. This arrhythmia occurs less frequently than AF but has similar precipitating factors, consequences, and drug therapy. On closer inspection, there may be a pattern of alternating 2:1, 3:1 and 4:1 conduction ratios The predominant mechanism of AF and atrial flutter is reentry, which is usually associated with organic heart disease that causes left atrial distention (eg, ischemia or infarction, hypertensive heart disease, and valvular disorders). Additional associated disorders include acute pulmonary embolus and chronic lung disease, resulting in pulmonary hypertension and cor pulmonale, and states of high adrenergic tone such as thyrotoxicosis, alcohol withdrawal, sepsis, and excessive physical exertion. Paroxysmal Supraventricular Tachycardia Caused by Reentry PSVT arising by reentrant mechanisms includes arrhythmias caused by AV nodal reentry, AV reentry incorporating an anomalous AV pathway, sinoatrial (SA) nodal reentry, and intraatrial reentry Rhythm strip demonstrating a regular, narrow-complex tachycardia VENTRICULAR ARRHYTHMIAS Premature Ventricular Complexes Ventricular Tachycardia Ventricular Proarrhythmia Ventricular Fibrillation Premature Ventricular Complexes Premature ventricular complexes (PVCs) can occur in patients with or without heart disease. Ventricular Tachycardia Monomorphic VT Torsades de Pointes Three or more repetitive PVCs occurring at a rate greater than 100 beats/min. A broad complex tachycardia originating from the ventricles. There are several different forms of VT — the most common is monomorphic VT, which originates from a single focus within the ventricles. ☐ Monomorphic:Wide QRS, Regular Rhythm ☐ Polymorphic( ex. Tdp) Wide QRS, irregular Rhythm It is a wide QRS tachycardia that may result acutely from severe electrolyte abnormalities (hypokalemia or hypomagnesemia), hypoxia, drug toxicity (eg, digoxin), or (most commonly) during an acute myocardial infarction (MI) or ischemia complicated by heart failure (HF). The chronic recurrent form is almost always associated with organic heart disease (eg, idiopathic dilated cardiomyopathy or remote MI with left ventricular [LV] aneurysm). Sustained VT is that which requires intervention to restore a stable rhythm or persists a relatively long time (usually >30 s). Nonsustained VT self-terminates after a brief duration (usually