Myocardial Infarction Lecture Notes PDF

MYOCARDIAL INFARCTION/ IHD CARDIOVASCULAR SYSTEM/PPOM 2 Maria M. Plummer, M.D. Associate Professor Department of Clinical Specialties Rockefeller Room #306 [email protected]  Session Objectives- see CPG for any updates 1. Describe and discuss the general concepts of ischemic heart d...

MYOCARDIAL INFARCTION/ IHD CARDIOVASCULAR SYSTEM/PPOM 2 Maria M. Plummer, M.D. Associate Professor Department of Clinical Specialties Rockefeller Room #306 [email protected]  Session Objectives- see CPG for any updates 1. Describe and discuss the general concepts of ischemic heart disease and define and compare stable, unstable, and Prinzmetal angina. 2. Explain the pathogenesis/mechanism of coronary thrombosis and how it leads to myocardial infarction and the initial changes of myocardial necrosis at the cellular and subcellular levels. 3. Discuss and describe the changes of myocardial infarct as the time sequence evolves in morphological and pathophysiological terms. 4. Correlate myocardial infarction changes with clinical and laboratory manifestations. 5. Discuss and describe complications of myocardial infarctions including arrhythmias, pericarditis, ventricular free wall rupture, true and false aneurysms, papillary muscle and septal rupture, and contractile dysfunction. Note: Learning objective 1 and 2 have been discussed in Atherosclerosis and will be Reviewed briefly in this session which will concentrate on objectives 2, 3, 4,and 5  Outline Review IHD Overview of Myocardial Infarction – Clinical: Symptoms – EKG/ECG changes – Biochemical markers Pathophysiology of Cellular Injury Gross and microscopic changes in MI Complications Practice questions  IHD - Syndromes Myocardial infarction, most significant form, where ischemia causes death of cardiac muscle Angina pectoris, where ischemia isn’t severe enough to cause infarction, but is often http://www.nhlbi.nih.gov/health/health- topics/topics/cad/signs precursor Chronic IHD with heart failure Sudden cardiac death http://health.wikinut.com/General-considerations- On-Ischemic-Heart-Disease/2-343gd5/ Robbins and Cotran, Pathological Basis of Diseases, 10th edition, 2020, Ch. 12  IHD – Consequences of Myocardial Ischemia Stable angina – Previously discussed, chest pain with physical activity Unstable angina – Previously discussed, chest pain at rest Prinzmetal angina – vasospasm- does not depend on exercise or rest Myocardial infarction – acute plaque change with total thrombotic occlusion, followed by myocardial death Sudden cardiac death – often due to a disrupted plaque producing ischemia which induces a fatal ventricular arrhythmia Robbins and Cotran, Pathological Basis of Diseases, 10th edition, 2020, Ch. 12  IHD - Pathogenesis Over 90% of patients with IHD have atherosclerosis within one or more coronary arteries Obstructions occupying 75% or more of the lumen cause symptoms induced by exertion 90% obstruction can lead to insufficient coronary blood flow even at rest Acute coronary syndrome #1 source of MI is acute plaque rupture of vulnerable or unstable plaque with thrombus formation Occurs via rupture, erosion, ulceration, and/or deep hemorrhage Often associated with intralesional inflammation, which mediates plaque disruption Robbins and Cotran, Pathological Basis of Diseases, 10th edition, 2020, Ch. 12  Myocardial Infarction Necrosis of cardiac myocytes (Irreversible) Usually due to rupture of an atherosclerotic plaque with thrombus - complete occlusion of coronary artery Leading cause of death in U.S Robbins and Cotran, Pathological Basis of Diseases, 10th edition,,  Myocardial Infarction Initial phase: Subendocardial necrosis involving 2 months Scarring complete Dense collagen scar Robbins, Pathologic Basis of Disease, 10th edition, 2020, pg. 547, Table 12-5  Normal Myocardium Central nuclei and syncytial arrangement of myocardial fibers Pale pink intercalated disks - help synchronize myocyte contraction via electrical coupling of adjoining cells. http://library.med.utah.edu/WebPath/webpath.html  Cellular Swelling: 0 to 30 minutes Acute and Reversible Ischemia causes decreased oxidative phosphorylation and decreased ATP Decreased function of Na+ pump and subsequent influx of H2O and Na+ resulting in cell swelling http://library.med.utah.edu/WebPath/webpath.html  Wavy fibers 30 minutes to about 4 hours http://library.med.utah.edu/WebPath/webpath.html  Early Coagulative Necrosis Edema – 4 to 12 hours Usually cannot see gross changes in heart if MI is less than 12 hours old Unless aided by use of TTC which stains normal myocardium brick-red and leaves infarcted area pale and unstained (loss of dehydrogenases) http://library.med.utah.edu/WebPath/webpath.html  Early Acute MI: 24 hours Increased loss of cross striations, some contraction bands are also seen, and the nuclei are undergoing karyolysis. Some neutrophils beginning to infiltrate , the myocardium. http://library.med.utah.edu/WebPath/webpath.html  Acute MI: 1-3 days Coagulative necrosis with loss of nuclei and striations, Interstitial infiltration of neutrophils http://library.med.utah.edu/WebPath/webpath.html  Acute MI: 1-3 days Acute myocardial infarction in the septum. After several days, yellowish center with necrosis and inflammation surrounded by hyperemic border. http://library.med.utah.edu/WebPath/webpath.html  Acute MI: 3-7 days Start of disintegration of dead myofibers, early phagocytosis of dead cells by macrophages http://library.med.utah.edu/WebPath/webpath.html  Acute MI: 7-10 days Below myocardial fibers (top) are many macrophages along with numerous capillaries and little collagenization Early granulation tissue formation http://library.med.utah.edu/WebPath/webpath.html  Acute MI: 2 weeks Healing MI Increased collagen, decreased cellularity or vascularity Grey-white scar, from border to center of infarct http://library.med.utah.edu/WebPath/webpath.html  Acute MI: 2 months Dense collagen scar http://library.med.utah.edu/WebPath/webpath.html  CONTRACTION BANDS Contraction bands - very eosinophilic transverse bands made of closely packed hypercontracted sarcomeres. Associated with reperfusion injury In myocardial infarction, most likely seen at the margin of infarct. Represent the effects of hypercontraction due to massive calcium influx across plasma membranes which increase actinomyosin interactions In the absence of ATP, sarcomeres cannot relax and “get stuck” in agonal tetanic state Contributing factors to reperfusion injury include mitochondrial dysfunction, myocyte hypercontracture, free radicals, leukocyte aggregation, platelet and complement activation Robbins and Cotran, Pathological Basis of Diseases, 10th edition, 2020, Ch. 12  Contraction Bands The myocardial fibers are beginning to lose cross striations; nuclei not clearly visible in most cells. Many irregular darker pink wavy contraction bands extend across the fibers. Reperfusion http://library.med.utah.edu/WebPath/webpath.html  Complications of MI (gross and microscopic) Cardiogenic shock (massive infarction), Congestive heart failure (Low EF) Arrhythmia (conduction disturbances and myocardial irritability) Acute fibrinous Pericarditis presents as chest pain with friction rub Rupture of Ventricular free wall leads to cardiac tamponade Rupture of Septum (leads to LV->RV shunt) Rupture of papillary muscle – severe, acute mitral regurgitation Ventricular Aneurysm - Mural thrombus: combo of local myocardial contractility abnormality (causing stasis) with endocardial damage (thrombogenic surface) Dressler syndrome - autoimmune pericarditis  Question A 55 year old man has sudden onset of severe substernal chest pain that radiates to the neck. On PE, he is afebrile but has tachycardia, hyperventilation, and hypotension. Auscultation reveals no cardiac murmurs. The patient undergoes emergent coronary angiography which shows a thrombotic occlusion of the left circumflex artery and 50 to 70 % narrowing in the proximal circumflex and anterior descending arteries. Which of the following complications of this disease is most likely to occur within one hour of these events? A. ventricular fibrillation B. Pericarditis C. Myocardial rupture D. Ventricular aneurysm E. Thromboembolism  Arrhythmias Major source of pre-hospital mortality Anatomic interruption of perfusion to structures of the conduction pathway Toxic metabolic products & abnormal transcellular ion concentrations Scar tissue Autonomic stimulation Usually occurs 4-24 hours post MI Robbins and Cotran, Pathological Basis of Diseases, 10th ed., 2020, Ch. 12  Arrhythmias Conduction Pathway Primary Arterial Supply SA Node RCA (70% of patients) AV Node RCA (85%) Bundle of His LAD (septal branches) RBB LAD (proximal portion) RCA (Distal portion) LBB Left anterior fascicle LAD Left posterior fascicle LAD and PDA  Acute Pericarditis Neutrophils are recruited to the site and degrade dying cells and ECM. They release metalloproteinases that degrade collagen and irritate the pericardium leading to acute fibrinous pericarditis Occurs within the first 2 - 3 days; gradually resolves over next few days http://library.med.utah.edu/WebPath/webpath.html  Pericarditis Clinical and Lab Findings Pericardial effusion- Muffled heart sounds Hypotension associated with pulsus paradoxus(abnormal drop in systolic blood pressure greater than 10mm Hg during inspiration) Neck vein distention CXR- “Water bottle” configuration Pericardial friction rub -Scratchy 3 component friction rub, best heard with the patient leaning forward ECG findings show diffuse ST segment elevation except VR and V1 and PR segment depression Commonly presents with sharp pain, aggravated by inspiration and relieved by sitting up and leaning forward Robbins and Cotran, Pathological Basis of Diseases, 10th edition, 2020, Ch. 12 https://radiopaedia.org/cases/pericardial-effusion-14 41  Dressler’s Syndrome Autoimmune induced fibrinous pericarditis occurring anywhere between 2nd week and 2nd month post MI Autoantibodies directed against damaged pericardial antigens Similar symptoms as acute pericarditis Robbins and Cotran, Pathological Basis of Diseases, 10th ed., 2020, Ch.12  Myocardial Rupture Myocardial rupture, most likely between 3-7 days following MI, when myocardium is softest – coagulative necrosis, neutrophilic infiltrate, and lysis of myocardial connective tissue weaken the infarcted myocardium Arrow marks point of rupture in this anterior-inferior MI of left ventricular free wall and septum http://library.med.utah.edu/WebPath/webpath.html  Rupture: Ventricular Free Wall Cardiac Tamponade - compression of heart by fluid (blood) in pericardium leading to decrease cardiac output Equilibration of diastolic pressure in all 4 chambers Findings: Becks Triad (hypotension, distend neck veins, distant heart sound) Increase in heart rate, Pulsus Paradoxus, Kussmaul sign (paradoxical rise in JVP on inspiration – indicates limited right ventricular filling) EKG: low voltage QRS and Electrical Alternans http://library.med.utah.edu/WebPath/webpath.html  False Aneurysm What if the rupture is incomplete? LV free wall held in check by thrombus that plugs the hole in the myocardium Epicardium and adherent parietal pericardium form “wall” http://library.med.utah.edu/WebPath/webpath.html  Question A 58 year old man suffered a myocardial infarction involving the apex of the left ventricle. Six months later, an echocardiogram shows the development of a ventricular bulge that does not contract during systole. The patient subsequently suffers a massive stroke and suddenly dies. Which of the following would be an expected finding at autopsy? A. Calcific aortic stenosis B. Dilated cardiomyopathy C. Mitral valve prolapse D. mural thrombus E. Ventricular rupture  True Ventricular Aneurysm Cross section through the heart reveals a ventricular aneurysm with a very thin wall at the arrow Note how the aneurysm bulges out The stasis in this aneurysm allows mural thrombus to form within the aneurysm. http://library.med.utah.edu/WebPath/webpath.html  True Ventricular Aneurysm Late complication of MI: weeks – months after Does NOT involve communication between the LV and the pericardium Usually does not rupture http://library.med.utah.edu/WebPath/webpath.html  Rupture: Papillary Muscle Rupture Leads to incompetent mitral valve (MR) Clinical Presentation: Blood backs up into lungs, transudation of fluid, shortness of breath, pansytolic murmur. Posteromedial LV papillary muscle most susceptible b/c of its more precarious blood supply Occlusion of RCA, in right dominant heart pt., ischemia to posterior LV 1/3 septum - where posterior leaflet of mitral valve attaches. http://library.med.utah.edu/WebPath/webpath.html  Rupture: Ventricular Septum Analogous to LV free wall rupture, but consequence and patient presentation are different Blood shunted LV → RV Pt presents with Right sided heart failure, JVD, pedal edema Loud systolic murmur at left sternal border, representing transeptal flow Most often associated with the LAD coronary artery thrombosis http://library.med.utah.edu/WebPath/webpath.html  Contractile Dysfunction Congestive heart failure – Left ventricular failure ↓ Contractility Cardiogenic shock - severely decreased cardiac output and hypotension ↑ Ischemia Hypotension Inadequate perfusion of peripheral tissues: CHF develops when more than ↓ Coronary 40% of the LV has infarcted perfusion pressure Robbins and Cotran, Pathological Basis of Diseases, 10th ed., 2020, Ch. 12  Pulmonary Edema and Congestion with Heart Failure Cells Blood is phagocytosed by alveolar macrophages Hemosiderin accumulates in alveolar macrophages called heart failure cells http://library.med.utah.edu/WebPath/webpath.html  MI Treatment Aspirin and or heparin – limits thrombosis Supplemental oxygen – minimize ischemia Nitrates – vasodilate coronary arteries (decrease preload = decrease stress) Beta-Blockers – slows heart rate, decreasing oxygen demand and risk for arrhythmia ACE Inhibitors – decrease LV dilation Fibrinolysis or angioplasty – opens blocked vessel Robbins and Cotran, Pathological Basis of Disease, 10th ed., 2020, Ch. 12  Question A 52 year old man with a history of diabetes mellitus and hypertension experiences pain in his left arm and shoulder for the past 2 hours. Over the next 6 hours he develops shortness of breath which continues for 2 days. On day 3 he sees his doctor who notes a normal temperature, a pulse of 82 bpm, respirations of 18 bpm, and blood pressure of 160/100 mm Hg. Lab studies at this time show that creatinine kinase serum levels are within normal limits but troponin I level is increased. The patient is admitted to the hospital and continues to have dyspnea for the next 3 days. On day 7 after the initial onset of shoulder pain, the patient has a cardiac arrest and does not survive resuscitative efforts. An autopsy performed shows a large transmural infarction of the left anterior free wall with rupture and hemopericardium. Which statement is most likely true?  Answer Choices A. Myocardial infarction did not develop until day 5 or 6 after the episode of shoulder pain B. The normal CK level on day 3 excludes the possibility of myocardial infarction within the preceding 72 hours C. the patient had an acute myocardial infarction on the day he developed shoulder pain D. A CK-MB level would have detected an acute MI on day 3 E. The patient had a second MI which caused a myocardial rupture on day 7  Review Questions What type of necrosis that occurs following MI? What type of cells infiltrate the myocardium 1- 3 days post-MI and 3-7 days post MI ?  Summary Slide Myocardial infarction – definition Subendocardial v. Transmural Frequency and sites EKG changes Time sequence changes – see text, power point slide for details 0-30 minutes reversible no real change 30 min – 4 hrs “wavy fibers” 4 – 12 hrs gross: focal mottling HISTO: edema, start coag necrosis 12 – 24 hrs: gross: dark mottling HISTO: coag necrosis, pyknosis, contraction bands, start PMNs 1 – 3 days: gross: yellow, tan center HISTO: neutrophil infiltration 3 – 7 days: gross: hyperemic border, central yellow-tan HISTO prominent macrophages, beginning granulation tissue 7 – 10 days: HISTO: granulation tissue prominent 2 weeks: HISTO: increased collagen formation 2 months – HISTO: well formed scar Laboratory tests/clinical correlation Complications – arrhythmias, pericarditis (acute fibrinous), pericarditis (Dressler syndrome), ventricular free wall rupture, false v. true aneurysm, papillary muscle rupture, ventricular septal rupture, contractile dysfunction  Reference Robbins and Cotran Pathologic Basis of Disease, 10th Edition, 2020 Douglas L. Mann, Murali Chakinala. Harrison's Principles of Internal Medicine. 19th edition. First Aid for USMLE  Lecture Feedback Form: https://comresearchdata.nyit.edu/redcap/surveys/?s=HRCY448FWYXREL4R