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Coronary artery diseases

  1. CAD Denis Katatwire MMED1-Internal Medicine
  2. Outline i. Introduction ii. Epidemiology iii. Aetiology iv. Pathophysiology v. Clinical presentation vi. Diagnosis. vii. Treatment
  3. Introduction • Coronary artery disease (CAD) is a pathological process characterized by atherosclerotic plaque accumulation in the epicardial arteries, whether obstructive or non-obstructive. • This process can be modified by lifestyle adjustments, pharmacological therapies, and invasive interventions designed to achieve disease stabilization or regression. • The disease can have long, stable periods but can also become unstable at any time, typically due to an acute atherothrombotic event caused by plaque rupture or erosion.
  4. Cont… • However, the disease is chronic, most often progressive, and hence serious, even in clinically apparently silent periods. • The dynamic nature of the CAD process results in various clinical presentations, which can be conveniently categorized as either i. Acute coronary syndromes (ACS) ii. Chronic coronary syndromes (CCS).
  5. Acute coronary syndromes (ACS) i. Unstable angina ii. ST- Elevation Myocardial infarction (STEMI) iii. Non ST-elevation Myocardial infarction (NSTEMI)
  6. Chronic coronary syndromes (CCS) i. Suspected CAD and ‘stable’ anginal symptoms, and/or dyspnoea ii. New onset of heart failure (HF) or LV dysfunction and suspected CAD iii. Asymptomatic and symptomatic with stabilized symptoms <1 year after an ACS, or patients with recent revascularization iv. Asymptomatic and symptomatic >1 year after initial diagnosis or revascularization v. Angina and suspected vasospastic or microvascular disease vi. Asymptomatic with CAD detected at screening
  7. Epidemiology • CAD is the commonest cause of deaths worldwide • Mortality rates have declined over the past four decades in western countries however this condition remains responsible for ~one-third of all deaths in individuals over age 35. • Mortality is on the rise in Low and middle income countries Tanzania being among • The 2016 Heart Disease and Stroke Statistics update of the AHA reported that 15.5 million people in the USA. have CHD. • The reported prevalence increases with age for both women and men. • For those US people, the lifetime risk of developing CHD with ≥2 major risk factors is 37.5% for men and 18.3% for women.
  8. Risk factors MODIFIABLE risk factors: • Hyperlipidemia (the most important risk factor) • Obesity • Diabetes mellitus • Hypertension • CKD • Sedentary lifestyle/Physical inactivity • Obesity • Diet: high caloric intake & increase in intake of saturated animal fats and hydrogenated vegetable fats, which contain atherogenic trans-fatty acids • Excess alcohol use • Smoking
  9. Cont… • NON-MODIFIABLE risk factors • Age • Sex: Male>Female before menopause, after menopause the risk may be the same or be higher in females • Family history of premature cardiac death/coronary artery disease
  10. Pathophysiology • Central to an understanding of the pathophysiology of myocardial ischemia is the concept of myocardial supply and demand. • In normal conditions, for any given level of a demand for oxygen, the myocardium will control the supply of oxygen-rich blood to prevent underperfusion of myocytes and the subsequent development of ischemia and infarction. • The major determinants of myocardial oxygen demand (MVO2) are heart rate, myocardial contractility, and myocardial wall tension (stress).
  11. Cont… • An adequate supply of oxygen to the myocardium requires a satisfactory level of oxygen-carrying capacity of the blood (determined by the inspired level of oxygen, pulmonary function, and hemoglobin concentration and function) and an adequate level of coronary blood flow. • Blood flows through the coronary arteries in a phasic fashion, with the majority occurring during diastole. • By reducing the lumen of the coronary arteries, atherosclerosis limits appropriate increases in perfusion when the demand for flow is augmented, as occurs during exertion or excitement.
  12. Cont… • >90% of patients with IHD have atherosclerosis of one or more of the coronary arteries. • When the luminal reduction is severe, myocardial perfusion in the basal state is reduced. • Coronary blood flow also can be limited by spasm, arterial thrombi, and, rarely, coronary emboli as well as by ostial narrowing due to aortitis. • Congenital abnormalities such as the origin of the left anterior descending coronary artery from the pulmonary artery may cause myocardial ischemia and infarction in infancy, but this cause is very rare in adults.
  13. Cont • Myocardial ischemia also can occur if myocardial oxygen demands are markedly increased and particularly when coronary blood flow may be limited, as occurs in severe left ventricular hypertrophy due to aortic stenosis. • The latter can present with angina that is indistinguishable from that caused by coronary atherosclerosis largely owing to subendocardial ischemia. • A reduction in the oxygen-carrying capacity of the blood, as in extremely severe anemia or in the presence of carboxyhemoglobin, rarely causes myocardial ischemia by itself but may lower the threshold for ischemia in patients with moderate coronary obstruction.
  14. Cont… • Not infrequently, two or more causes of ischemia coexist in a patient, such as an increase in oxygen demand due to left ventricular hypertrophy secondary to hypertension and a reduction in oxygen supply secondary to coronary atherosclerosis and anemia. • Abnormal constriction or failure of normal dilation of the coronary resistance vessels also can cause ischemia. When it causes angina, this condition is referred to as microvascular angina.
  15. The process of coronary atherosclerosis Initiation of atherosclerosis • The major risk factors for atherosclerosis: high levels Of LDL, low HDL, cigarette smoking, hypertension, and diabetes mellitus impair the normal functions of the endothelium by activating the pro inflammatory pathways resulting in endothelial cell activation and dysfunction = impaired functions include local control of vascular tone, maintenance of an antithrombotic surface, and control of inflammatory cell adhesion and diapedesis.
  16. Cont… • This causes the formation of initial lesions of atherosclerosis where the “fatty streak” are deposited on the intima. • In the long run, the loss of normal endothelial functions leads to inappropriate constriction, luminal thrombus formation, and abnormal interactions between blood cells especially monocytes and platelets, and the activated vascular endothelium. • Functional changes in the vascular milieu ultimately result in the subintimal collections of fat, smooth muscle cells, fibroblasts, and intercellular matrix that define the atherosclerotic plaque.
  17. Cont… • This process develops at irregular rates in different segments of the epicardial coronary tree and leads eventually to segmental reductions in cross-sectional area. • This process commonly occurs at the sites of increased turbulence in coronary flow, such as at branch points in the epicardial arteries. • Slowly developing occlusions may stimulate collateral vessels over time = ANGIOGENESIS, which protect against distal myocardial ischemia and infarction even with an eventual high-grade stenosis.
  18. Cont… • With progressive worsening of a stenosis in a proximal epicardial artery, the distal resistance vessels (when they function normally) dilate to reduce vascular resistance and maintain coronary blood flow. • A pressure gradient develops across the proximal stenosis, and poststenotic pressure falls. When the resistance vessels are maximally dilated, myocardial blood flow becomes dependent on the pressure in the coronary artery distal to the obstruction.
  19. Cont… • In these circumstances, ischemia, manifest clinically by angina or electrocardiographically by ST-segment deviation, can be precipitated by increases in myocardial oxygen demand caused by physical activity, emotional stress, and/or tachycardia. • Changes in the caliber of the stenosed coronary artery due to physiologic vasomotion, loss of endothelial control of dilation (as occurs in atherosclerosis), pathologic spasm (Prinzmetal’s angina), or small platelet-rich plugs also can upset the critical balance between oxygen supply and demand and thereby precipitate myocardial ischemia.
  20. Cont... • A fixed obstructive lesion of 75% or greater (i.e., only 25% or less lumen remaining) generally causes symptomatic ischemia induced by exercise; with this degree of obstruction, the augmented coronary flow provided by compensatory vasodilation is no longer sufficient to meet even moderate increases in myocardial demand. • A 90% stenosis can lead to inadequate coronary blood flow even at rest.
  21. Cont… • Although only a single major coronary epicardial trunk may be affected, two or all three—lateral anterior descending (LAD), left circumflex (LCX), and right coronary artery (RCA)— are often involved. • Clinically significant stenosing plaques may be located anywhere within these vessels but tend to predominate within the first several centimetres of the LAD and LCX and along the entire length of the RCA.
  22. Role of Acute Plaque Change; • In most patients the myocardial ischemia underlying unstable angina, acute MI, and (in many cases) sudden cardiac death is precipitated by abrupt plaque change followed by thrombosis • Thus, these important manifestations are termed the acute coronary syndromes. • Most often, the initiating event is disruption of previously only partially stenosing plaques with any of the following: i. Rupture/fissuring, exposing the highly thrombogenic plaque constituents ii. Erosion/ulceration, exposing the thrombogenic subendothelial basement membrane to blood. iii. Hemorrhage into the atheroma, expanding its volume.
  23. Atherosclerotic Plaque: • = Focal accumulation of smooth muscle cells, foam cells, cholesterol crystals and lipid under the endothelium of the artery (within the Tunica Intima). • Given time, this plaque can protrude into the lumen of the vessel reducing blood flow • Often develops at branch points or curves within the vasculature….. Therefore blood is slowed and/or turbulent. • As the atheroma within the coronary arteries enlarges, the blood flow to the heart decreases and therefore so does the O2 supply • The heart is not in danger of hypoxia until 50% of the vessel is occluded.
  24. Cont... • As the heart senses a decrease in O2, there is attempted compensation: i. Increase Heart Rate ii. Increase Blood Pressure iii. THE two above = Aggravation/Worsening of the atheroma • When 70-75% of the artery is occluded, Angina Pectoris will occur with exertion.
  25. Cont… • The events that trigger abrupt changes in plaque configuration and superimposed thrombosis are complex and poorly understood. • Influences, both intrinsic (e.g., plaque structure and composition) and extrinsic (e.g., blood pressure, platelet reactivity) are important. • Acute alterations in plaque imply the inability of a plaque to withstand mechanical stresses. • The structure and composition of a plaque are dynamic and contribute to a propensity to disruption.
  26. Cont…… • Plaques that contain large areas of foam cells and extracellular lipid, and those in which the fibrous caps are thin or contain few smooth muscle cells or have clusters of inflammatory cells, are more likely to rupture, and are therefore called "vulnerable plaques." • Fissures frequently occur at the junction of the fibrous cap and the adjacent normal plaque-free arterial segment, a location at which the blood flow-inducing mechanical stresses within the plaque are highest and the fibrous cap is thinnest.
  27. Cont… • It is now recognized that the fibrous cap can undergo continuous remodelling. • The balance of synthetic and degradative activity of collagen, the major structural component of the fibrous cap, accounts for its mechanical strength and determines plaque stability and prognosis. • Collagen is produced by smooth muscle cells and degraded by the action of metalloproteinases, enzymes elaborated by macrophages in atheroma.
  28. Cont… • Thus, there is considerable evidence that inflammation destabilizes the mechanical integrity of plaques since macrophages increase the levels of metalloproteinases thinning the fibrous cap of the atheromatous plaque. • Moreover, drugs such as statins (inhibitors of HMG Co-A reductase, a key enzyme in the synthesis of cholesterol) that reduce clinical events associated with IHD, are thought to stabilize plaques by their lipid-lowering effect, as well as by reducing plaque inflammation.
  29. Cont… • Influences extrinsic to plaque are also important. Adrenergic stimulation can elevate physical stresses on the plaque through systemic hypertension or local vasospasm. • Indeed, the adrenergic stimulation associated with awakening and arising induces a pronounced circadian periodicity for the time of onset of acute MI, with a peak incidence between 6 a.m. and 12 noon, concurrent with a surge in blood pressure and immediately following heightened platelet reactivity.
  30. Cont…. • Intense emotional stress can also contribute to plaque disruption; this is most dramatically illustrated by the marked increase in the incidence of sudden death that is associated with natural or other disasters such as earthquakes • It is now recognized that the pre-existing culprit lesion in patients who develop myocardial infarction and other acute coronary syndromes is not necessarily a severely stenotic and hemodynamically significant lesion prior to its acute change.
  31. Cont… • Pathologic and clinical studies show that plaques that undergo abrupt disruption leading to coronary occlusion often are those that previously produced only mild to moderate luminal stenosis. • ~2/3 of plaques that rupture with subsequent occlusive thrombosis caused occlusion of only 50% or less before plaque rupture, and 85% had initial stenosis less than 70%. • Thus, the worrisome conclusion is that a rather large number of now asymptomatic adults in the industrial world have a real but unpredictable risk of a catastrophic coronary event.
  32. Cont…… • Regrettably, it is presently impossible to reliably predict plaque disruption or subsequent thrombosis in an individual patient. • Accumulating evidence indicates that plaque disruption and the ensuing platelet aggregation and intraluminal thrombosis are common, repetitive, and often clinically silent complications of atheroma. • Moreover, healing of subclinical plaque disruption and overlying thrombosis is an important mechanism of growth of atherosclerotic lesions.
  33. Role of Inflammation • Inflammatory processes play important roles at all stages of atherosclerosis, from its inception to the development of complications. • The establishment of the initial lesion requires the interaction between endothelial cells and circulating leukocytes, leading to the accumulation of T cells and macrophages in the arterial wall. • Entry of leukocytes into the wall is a consequence of the release of chemokines by endothelial cells, and the increased expression of adhesion proteins (ICAM-1, VCAM-1, E-selectin and P-selectin) in these cells.
  34. Cont…… • T cells located in the arterial wall produce cytokines such as TNF, IL-6 and IFN-γ that stimulate endothelial cells and activate macrophages, which become loaded with oxidized LDL. At later stages of atherosclerosis, destabilization and rupture of the plaque may involve the secretion of metalloproteinases by macrophages…… These enzymes weaken the plaque by digesting collagen at the fibrous cap or the shoulder of the lesion. • Because of the important role of inflammation in the pathogenesis of atherosclerosis, several proteins involved in inflammation may serve as potential markers of atherosclerosis = CRP), an acute phase reactant made in the liver, has been suggested as a predictor of risk of coronary heart disease.
  35. Role of Coronary Thrombus • Partial or total thrombosis associated with a disrupted plaque is critical to the pathogenesis of the acute coronary syndromes. • In the most serious form, acute transmural MI, thrombus superimposed on a disrupted but previously only partially stenotic plaque converts it to a total occlusion. • In contrast, with unstable angina, acute subendocardial infarction, or sudden cardiac death, the extent of luminal obstruction by thrombosis is usually incomplete (mural thrombus), and it may wax and wane with time.
  36. Cont…. • Mural thrombus in a coronary artery can also embolize. Indeed, small fragments of thrombotic material in the distal intramyocardial circulation or microinfarcts may be found at autopsy of patients who have had unstable angina or sudden death. • Finally, thrombus is a potent activator of multiple growth- related signals in smooth muscle cells, which can contribute to the growth of atherosclerotic lesions
  37. • Vasoconstriction compromises lumen size, and, by increasing the local mechanical forces, can potentiate plaque disruption. • Vasoconstriction at sites of atheroma is stimulated by: i. Circulating adrenergic agonists ii. Locally released platelet contents iii. Impaired secretion of endothelial cell relaxing factors relative to contracting factors (e.g., endothelin) due to atheroma-associated endothelial dysfunction , and possibly iv. Mediators released from perivascular inflammatory cells.
  38. Cont... • The acute coronary syndromes—angina, acute MI, and sudden death—share a common pathophysiologic basis in coronary atherosclerotic plaque disruption and associated intraluminal platelet-fibrin thrombus formation. • The critical consequence is downstream myocardial ischemia. • Stable angina results from increases in myocardial oxygen demand that outstrip the ability of markedly stenosed coronary arteries to increase oxygen delivery but is not usually associated with plaque disruption.
  39. Cont….. • Unstable angina derives from a sudden change in plaque morphology, which induces partially occlusive platelet aggregation or mural thrombus, and vasoconstriction leading to severe but transient reductions in coronary blood flow. • In some cases, distal microinfarcts occur secondary to thromboemboli. In MI, acute plaque change induces total thrombotic occlusion. • Finally, sudden cardiac death frequently involves a coronary lesion in which disrupted plaque and often partial thrombus and possibly embolus have led to regional myocardial ischemia that induces a fatal ventricular arrhythmia.
  40. Subendocardial infarction • Involves a small area in the subendocardial wall of the left ventricle, ventricular septum or papillary muscles. • Subendocardial area is particularly susceptible to ischaemia • Being the innermost layer/subendocardium, is preferentially injured first • ECG: ST segment depression
  41. Transmural infarction • Associated with atherosclerosis involving a major coronary artery. • It extend through the whole thickness of the heart muscle and usually a result of complete occlusion of the area’s blood supply • ECG: ST segment elevation and Q waves
  42. Clinical presentation • In ~50%, a precipitating factor appears to be vigorous physical exercise, emotional stress, or a medical or surgical illness. • Circadian variations have been reported such that clusters are seen in the morning within a few hours of awakening (highly likely to autonomic activation observed with cardiac rhthym). • Chest pain of the angina nature: i. Most common presenting complaint ii. Heavy, squeezing, and crushing, sometimes as stabbing or burning iii. Severe iv. Lasts longer… around 30 minutes
  43. Cont… v. Central portion of the chest and/or the epigastrium, and, on occasion, it radiates to the back, neck, lower jaw and arms. Less common sites of radiation include the abdomen, back, lower jaw, and neck. vi. Often accompanied by weakness, sweating, nausea, vomiting, anxiety, and a sense of impending doom. vii. Occurs at rest
  44. Atypical/asymptomatic presentation • Diabetes mellitus • Old age • Female sex • Inferior MI
  45. Physical exam • Anxious and restless • Levine sign • Diaphoresis • Tachycardia and/or hypertension • 4th and 3rd heart sounds may be heard • Pericardial friction rub - ??transmural STEMI • Reduced volume of carotid pulse • Temperature elevations up to 38°C 1st week after STEMI. • Hypotension/shock
  46. Diagnosis • Thorough hx taking • Thorough P. Exam • Laboratory findings i. Cardiac biomarkers ii. ECG iii. ECHO
  47. Cont… • MI progresses through the following temporal stages/MI Evolution: i. Acute (first few hours–7 days) ii. Healing (7–28 days) iii. Healed (≥29 days).
  48. Serum cardiac biomarkers • Cardiac-specific troponin T (cTnT) and cardiac-specific troponin I (cTnI): i. Is a contractile protein that is normally not found in serum ii. Released only when myocardial necrosis occurs iii. +ve troponin levels are considered virtually diagnostic of MI iv. Preferred biochemical markers for MI because Cardiomyocytes has more troponin than CK-MB per gram therefore high specificity and sensitivity v. Serum levels increase within 3 – 12 hrs. from the onset of chest pain, peak 24 – 48 hrs vi. Remain elevated for 7–10 days after STEMI
  49. Cont… • CK levels: 3 CK isoenzymes are as follows: i. CK with muscle subunits (CK – MM) = skeletal muscles ii. CK with brain subunit (CK – BB) = brain iii. CK – MB, which is found predominantly in the heart iv. CK – MB levels increase within 4-8 hrs of the onset of chest pain, reach peak values within 24 hrs, and return baseline after 48 – 72 hrs. v. Therefore it rises early and return to baseline early compared to Troponins can enable early detection of MI and show resolution of MI early compared to Troponins
  50. Cont… • Other markers may be sensitive but not specific: i. Myoglobin ii. ESR iii. PMNs Leukocytosis on FBP
  51. ECG Findings
  52. ECG findings of Unstable Angina • Normal ST or ST segment depression 0f >_0.05mV or 1/2 small box in 2 contiguous leads of the same territory • T-wave inversion of >_0.1mV
  53. ECG findings of NSTEMI • Normal ST or ST segment depression 0f >_0.05mV or 1/2 small box in 2 contiguous leads of the same territory • T-wave inversion of >_0.1mV
  54. ECG findings of STEMI • ST segment elevation 0f >_2mm in 2 contiguous precordial leads and >_1 mm in 2 adjacent limb leads • Nature of ST-Elevation: Convex (remember acute pericarditis cause diffuse concave ST segment elevation) • Secondary/Reciprocal changes in the other leads: ST depression and T wave changes • LBBB: • Dead man sign
  55. ECHO i. RMWA ii. LV function: E. function iii. RV infarction iv. Ventricular aneurysm v. Pericardial effusion vi. LV thrombus vii. Ventricular septal defect
  56. Cont… i. Radionuclide imaging techniques: less sensitivity and specificity for STEMI ii. MRI Imaging
  57. Exercise Stress Test; • Used to confirm diagnosis of angina Criteria for +ve stress test: • > 2mm ST segment depression • Hypotension defined by decrease of more than 10mmHg in SBP • Contraindications: • If the patient has chest pain now • Patient cant do exercise • Baseline abnormalities (LBBB, LVH, pace maker) • +++Cardiac imaging; coronary angiogram can be used to definitively diagnose or rule out coronary artery disease.
  58. Mechanical complications of ACS 1. Rupture of the left ventricular free wall: Fibrinolytic therapy, No history of previous angina or MI, ST-segment elevation or Q wave development on the initial electrocardiogram (ECG), Peak MB-creatine kinase above 150 international units/L are known risk factors • Usually leads to hemopericardium and death from cardiac tamponade… first suggested by the development of sudden profound right heart failure and shock. Emergent pericardiocentesis will confirm the diagnosis and transiently relieve the tamponade. Transthoracic echocardiography can further confirm the diagnosis Rx: ECHO-guided pericardiocentesis & Surgery
  59. Cont… 2. Rupture of the interventricular septum: risk factors are single-vessel disease (especially LAD), extensive myocardial damage, and poor septal collateral circulation. • Present with the precipitous onset of hemodynamic compromise characterized by hypotension, biventricular failure (often predominantly right-sided failure), and a new murmur (harsh, loud, and holosystolic) • Rx: Surgical repair
  60. Cont… 3. Mitral regurgitation • Caused by ischemic papillary muscle displacement, left ventricular dilatation or true aneurysm, and papillary muscle or chordal rupture. • Some patients with moderate to severe MR (but without papillary muscle rupture) are hemodynamically stable. Many such patients improve with medical therapy and revascularization (by fibrinolysis or primary angioplasty); a minority will eventually require mitral valve repair or replacement with coronary artery bypass grafting
  61. Cont… 4. Ventricular dilatation 5. Ventricular aneurysm
  62. Non mechanical complications of ACS • Congestive heart failure/LV failure • RV failure with: jugular venous distention, Kussmaul’s sign, hepatomegaly with or without hypotension. • Cardiogenic shock • Arrhythmias: i. PVC ii. VT iii. VF (commonest cause of death within the 1st 24 hours of onset of symptoms with ½ of them occurring within the 1st hour) iv. SVT v. AV/intraventricular conduction disturbances • Pericarditis • Thromboembolism
  63. Differential dx i. Acute pericarditis ii. Pulmonary embolism iii. Acute aortic dissection iv. Costochondritis v. PUD/Gastritis vi. Oesophagitis
  64. Management
  65. Cont… • Emergency ECG: and interpretation • Resuscitation, ACLS, Defibrillation for VF • Aspirin: Rapid inhibition of cyclooxygenase-1 in platelets followed by a reduction of thromboxane A2 levels is achieved by buccal absorption through chewing 300mg START Then 75mg daily…. For lifetime unless contraindicated • The same for CLOPIDEGROL..DUAT..Up to a year…then ASA For Life time unless patient contraindicated • Oxygen therapy if SPO2 is less than 90%
  66. Role of glucocorticoids and NSAIDs • With the exception of aspirin, they should be avoided in patients with STEMI. • They can impair infarct healing and increase the risk of myocardial rupture, and their use may result in a larger infarct scar. • In addition, they can increase coronary vascular resistance, thereby potentially reducing flow to ischemic myocardium.
  67. Cont… • Sublingual nitroglycerin: Up to three doses of 0.4 mg should be administered at about 5-min intervals: decrease chest discomfort: decrease myocardial oxygen demand & increasing myocardial oxygen supply: contraindicated with bradycardia and shock/hypotension • ……… contraindicated who used phosphodiesterase-5 inhibitor sildenafil/tadalafil for erectile dysfunction within the preceding 24 h, because it may potentiate the hypotensive effects of nitrates. An idiosyncratic reaction to nitrates, consisting of sudden marked hypotension, sometimes occurs but can usually be reversed promptly by the rapid administration of ??intravenous atropine.
  68. Cont… • Morphine: ANALGESIA, reduce sympathetically mediated arteriolar and venous constriction, and the resulting venous pooling may reduce cardiac output and arterial pressure. Morphine also has a vagotonic effect and may cause bradycardia or advanced degrees of heart block, particularly in patients with inferior infarction. These side effects usually respond to atropine (0.5 mg intravenously). Every 5 min intravenous injection of small doses (2–4 mg). • Beta blockers = useful in the control of the pain of STEMI by diminishing myocardial O2 demand and hence ischemia, reduce the risks of reinfarction and ventricular fibrillation. Contraindicated if the patients signs of AHF, Bradycardia, Hypotension/Cardiogenic shock, Heart block. Carvedilol, metoprolol
  69. Cont… • CCBs: Amlodipine/nifedipine are of little use however they very important in case of Prinzmetal's angina
  70. Reperfusion therapy • When ST-segment elevation of at least 2 mm in 2 contiguous precordial leads and 1 mm in 2 adjacent limb leads is present, a patient should be considered a candidate for reperfusion therapy that is selecting patients for fibrinolysis versus primary PCI (angioplasty, or stenting). • CABG can be done if the anatomy of coronary disease is complex, there is recurrent angina despite primary PCI is or as an elective procedure after resolution of the ACS • In the absence of ST-segment elevation, fibrinolysis is not helpful, and evidence exists suggesting that it may be harmful
  71. Cont… • Reperfusion in patients with STEMI can be accomplished by the pharmacologic (fibrinolysis) or catheter-based (primary PCI) approaches. • Implementation of these strategies varies based on the mode of transportation of the patient and capabilities at the receiving hospital. • Transport time to the hospital is variable from case to case, but the goal is to keep total ischemic time within 120 min. There are three possible scenarios: i. If EMS has fibrinolytic capability and the patient qualifies for therapy, prehospital fibrinolysis should be started within 30 min of EMS arrival on scene.
  72. Cont… ii. If EMS is not capable of administering prehospital fibrinolysis and the patient is transported to a non-PCI- capable hospital, the hospital door-to-needle time should be within 30 min for patients in whom fibrinolysis is indicated. iii. If EMS is not capable of administering prehospital fibrinolysis and the patient is transported to a PCI-capable hospital, the hospital door-to-balloon time should be within 90 min. Interhospital transfer : It is also appropriate to consider emergency interhospital transfer of the patient to a PCI-capable hospital for mechanical revascularization if:
  73. Cont… (1) there is a contraindication to fibrinolysis (2) PCI can be initiated promptly (within 90 minutes after the patient presented to the initial receiving hospital or within 60 min compared to when fibrinolysis with a fibrin-specific agent could be initiated at the initial receiving hospital) (3) Fibrinolysis is administered and is unsuccessful (i.e., “rescue PCI”). Secondary nonemergency interhospital transfer can be considered for recurrent ischemia. (4) If the patient arrives at a non-PCI-capable hospital, the door-to-needle time should be within 30 min. If the patient arrives at a PCI-capable hospital, the door-to-balloon time should be within 90 min.
  74. Fibrinolysis • Indicated for STEMI when the door to balloon time is more >_90 minutes or when PCI can not be done • 4 types of thrombolytics: i. tissue plasminogen activator (rtPA) ii. Streptokinase iii. Urokinase iv. Anistreplase
  75. Cont… • Streptokinase 250,000IU infusion over 30minutes, then 100,000IU per hour for 24hours OR Alteplase (rtPA) 100mg IV infusion over 2hours
  76. Absolute Contraindicationsto thrombolytictherapy: • Haemorrhagic cerebrovascular accidents (CVA) • Intracranial neoplasia, recent cranial surgery or trauma within 1 month Uncontrolled severe hypertension because of an increased risk of intracranial bleeding. • Major thoracic or abdominal surgery within 10days • Prolonged cardiopulmonary resuscitation • Current severe bleeding from gastrointestinal tract (GIT) or other organs • Known bleeding disorders
  77. Cont… Complications of thrombolytic therapy: 1. Allergy (Anaphylaxis) 2. Embolism 3. Major bleeding: i. Thrombolytic agent should be stopped ii. Fresh frozen Plasma administered iii. Tranexamic acid administered iv. Fibrinogen should be assayed for possible replacement.
  78. Cont... Anticoagulation: • Unfractionated Heparin (UFH) 10,000units IV bolus, then maintenance infusion starts with 6,000U over 6hours to keep PTT or clotting time 2-3 times above baseline. • PTT should be performed 12hourly according to lab instruction. • In patients with grossly impaired renal function (CrCl<20 ml/min),, UFH is an option for anticoagulation.
  79. Cont… Monitoring • UFH is monitored using the aPTT (2-3 x normal) or antiXa. • Monitoring should be done 6 hourly until 2 consecutive therapeutic results are obtained and 24 hourly thereafter. • Heparin should be started concurrently with warfarin and continued for at least 5 days after start of warfarin. • Heparin should not be discontinued until 2 consecutive therapeutic INR of 2-3 is achieved at least 24 hours apart (but not before day 5 of overlap).
  80. Cont… Complications: • Bleeding -ANTIDOTE: protamine sulfate slow infusion = 1mg for every 100 units of heparin (those infused in few past hours) - Protamine sulphate can cause more bleeding by causing platelet aggregation leading to thrombocytopenia. • HIT: ~0.5% (medical patients) - 3 % (after major surgery) MECHANISM: Heparin-induced production of antibodies against heparin-platelet factor 4 complexes. The formed antibodies cause platelets activation resulting in a prothrombotic state. The antibodies also cause endothelial activation. Thrombocytopenia is largely due to clearance of activated platelets by reticulo-endothelial system
  81. Cont… • Suspected cases should be screened with the 4T (Thrombocytopenia, Timing of Platelet count fall, Thrombosis or other sequelae and other causes of thrombocytopenia) pretest. • If positive, further use of UFH should be stopped. • Since paradoxical thrombosis continues in spite of the thrombocytopenia, anticoagulation should be continued with either a Bivalirudin, fondaparinux or DOAC. • The risk of HIT is 10 times with UFH>LMWH
  82. Cont.. Low Molecular weight Heparin (LMWH) • Enoxaparin 1mg/kg twice daily • LMWH forms a complex with antithrombin III therefore inactivating factor Xa and to a lesser extent activated factor II (FIIa) • Can accumulate in patients with impaired renal function (enoxaparin > dalteparin > tinzaparin). • Requires serum creatinine, FBC, PT and APTT • Enoxaparin should be avoided in patients with CrCl of <20ml/min.
  83. Cont… LMWH-Adverse effects: • Bleeding =Protamine sulphate reverses ~60% of anticoagulant activity of LMWH. If the last dose of LMWH is within 8 hours, protamine sulfate should be given at a dose of 1mg per 100 antiFXa units up to a maximum of 50mg (1mg of enoxaparin corresponds approximately to 100 antiFXa units) If over 8 hours has elapsed before the last administration of LMWH, a lower dose of protamine sulfate may be given (0.5mg per 100 antiFXa units). • HIT: - Use alternative anticoagulant Bivalirudin, fondaparinux or DOAC
  84. Cont… Fondaparinux • Synthetic heparin-like anticoagulant with reversible selective antithrombin (AT) dependent antiFXa activity. • Indications…. previous history of HIT anticoagulants • 5mg daily for <50kg, at 7.5mg daily for patients weighing 50- 100kg, while >100kg at 10mg daily, all by subcutaneous route. • To be avoided in patients with CrCl of <30ml/min. Warfarin should be commenced concurrently with fondaparinux and continued for at least 5 days, not discontinued until 2 consecutive therapeutic INR of 2-3 is achieved at least 24 hours apart.
  85. Cont… VIKA • Warfarin =Inhibition of vitamin K epoxide reductase and vitamin K reductase resulting into inhibition of gamma carboxylation required for carboxylation of the coagulation proteins factors II, VII, IX and X, as well as the anticoagulatory proteins C and S. • Must be initiated with a rapidly acting anticoagulant (UFH or LMWH) and after 5 or more days when the necessary anticoagulant effect of warfarin is achieved for most conditions. • Dosage: 5-10mg
  86. Cont… Monitoring treatment: • Use PT (and/or INR) • INR is checked daily as from day 3 of warfarin initiation and dosage adjusted until a stable therapeutic effect is achieved. • Targeted INR range is 2-3 • After stabilizing can be assessed at 4-6-8 weeks interval • A higher INR is recommended for patients with mechanical heart valve replacement and those with failed anticoagulant therapy despite well-documented INR values in range of 2-3.
  87. Cont… Complications: • Bleeding: =Serious bleeding and major overdose may require factor replacement and intravenous administration of vitamin K. • skin necrosis • Purple toe syndrome • Rash • Hepatitis.
  88. Cont… Direct Orally-active Anticoagulants (DOACs): • DOACs exhibit a comparable efficacy and a significantly lower bleeding risk when compared with warfarin • They can be administered once or twice daily without need for monitoring. • They have fewer clinically related drug interactions • They have fast onset of action like the LMWH and can replace these parenteral agents. • Initial heparin anticoagulation not required for rivaroxaban but initial higher doses of anticoagulant must be given in the 1st few weeks of therapy.
  89. Cont… • Two groups of DOACS i. Direct Factor Xa inhibitors: Rivaroxaban, apixaban (these two have an antidote: Andexanet alfa; a modified factor Xa), edoxaban, -Monitoring: Possible aFXa Test i. Direct Thrombin inhibitors: Dabigatran (Idarucizumab is the antidote of choice), Argatroban -possible monitoring Thrombin Time (TT)
  90. Long term therapy • Lifestyle interventions and risk factors control i. Smoking cessation ii. Optimal BP control iii. Diet advice = DASH Diet iv. Weight control with target of BMI of 22.5-25kg/m2 v. Encouraging physical activity: 30 minutes per day/150 per week of vigorous exercise/300 minutes of moderate intensity exercise vi. Moderation of alcohol use (limit their consumption to 14 units per week and women to 8 units per week (1 unit is equal to 125 mL of wine or 250 mL of beer)) vii. Adherence to prescribed treatment
  91. Pharmacotherapy • Antiplatelet therapy with low-dose aspirin (75–100 mg) is indicated (IA). • DAPT in the form of aspirin plus ticagrelor or prasugrel (or clopidogrel if ticagrelor or prasugrel are not available or are contraindicated), is recommended for 12 months after PCI, unless there are contraindications such as excessive risk of bleeding (IA). • A PPI in combination with DAPT is recommended in patients at high risk of gastrointestinal bleeding (IB). • In patients with an indication for oral anticoagulation, oral anticoagulants are indicated in addition to antiplatelet therapy (IC).
  92. Cont… • In patients who are at high risk of severe bleeding complications, discontinuation of P2Y12 inhibitor therapy after 6 months should be considered (IIaB) • In STEMI patients with stent implantation and an indication for oral anticoagulation, triple therapy should be considered for 1–6 months (according to a balance between the estimated risk of recurrent coronary events and bleeding) (Iia C) • DAPT for 12 months in patients who did not undergo PCI should be considered unless there are contraindications such as excessive risk of bleeding (IIa C)
  93. Cont… • In patients with LV thrombus, anticoagulation should be given for up to 6 months guided by repeated imaging IIa C • In high ischaemic-risk patients who have tolerated DAPT without a bleeding complication, treatment with DAPT in the form of ticagrelor 60 mg twice a day on top of aspirin for longer than 12 months may be considered for up to 3 years (IIb B) • In low bleeding-risk patients who receive aspirin and clopidogrel, low-dose rivaroxaban (2.5 mg BID) may be considered ( IIb B) • The use of ticagrelor or prasugrel is not recommended as part of triple antithrombotic therapy with aspirin and oral anticoagulation (III C)
  94. B-Blockers • Oral treatment with beta-blockers is indicated in patients with heart failure and/or LVEF <_40% unless contraindicated • Intravenous beta-blockers should be considered at the time of presentation in patients undergoing primary PCI without contraindications, with no signs of acute heart failure, and with an SBP >120 mmHg • Routine oral treatment with beta-blockers should be considered during hospital stay and continued thereafter in all patients without contraindications • Intravenous beta-blockers must be avoided in patients with hypotension, acute heart failure or AV block, or severe bradycardia.
  95. Lipid lowering therapies • It is recommended to start high-intensity Statin therapy as early as possible, unless contraindicated, and maintain it long term. • LDL-C goal of < 1.8 mmol/L (70 mg/dl) or a reduction of at least 50% if the baseline LDL-C is between 1.8–3.5 mmol/L (70–135 mg/dl) is recommended. • It is recommended to obtain a lipid profile in all STEMI patients as soon as possible after presentation. • In patients with LDL-C >_1.8 mmol/L (70 mg/dl) despite a maximally tolerated statin dose who remain at high risk, further therapy to reduce LDL-C should be considered.
  96. ACE inhibitors/ARBs • ACE inhibitors are recommended, starting within the first 24 h of STEMI in patients with evidence of heart failure, LV systolic dysfunction, diabetes, or an anterior infarct. • An ARB, preferably valsartan, is an alternative to ACE inhibitors in patients with heart failure and/or LV systolic dysfunction, particularly those who are intolerant of ACE inhibitors. • ACE inhibitors should be considered in all patients in the absence of contraindications
  97. MRAs • MRAs are recommended in patients with an LVEF <_40% and heart failure or diabetes, who are already receiving an ACE inhibitor and a beta-blocker, provided there is no renal failure or hyperkalaemia.
  98. ?? • Killip score and its importance • TIMI score and its applications
  99. References • Harrison's Principles of Internal Medicine; 18Th Edition • ESC Guidelines for CAD • AHA/ACC guidelines on CAD