Lecture 7: Ischemic Heart Diseases PDF

Pathophysiology PHMU 534 Lecture 7 Ischemic Heart Diseases Prof. Dr. Nabila Hamdi MD, PhD in Molecular Medicine and Pathology  Outline I. Overview II. Angina Pectoris  Typical or stable angina  Prinzmetal or variant angina  Unstable angina III....

Pathophysiology PHMU 534 Lecture 7 Ischemic Heart Diseases Prof. Dr. Nabila Hamdi MD, PhD in Molecular Medicine and Pathology  Outline I. Overview II. Angina Pectoris  Typical or stable angina  Prinzmetal or variant angina  Unstable angina III. Myocardial Infarction  Epidemiology  Pathogenesis  Clinical Features  Electrocardiographic Abnormalities  Laboratory Evaluation  Clinical Consequences & Complications 2  Competencies Demonstrate understanding of the pathophysiological mechanisms of various ischemic heart diseases. Utilize the proper medical terms in pharmacy practice. Integrate knowledge from fundamental sciences to relate the mechanisms of ischemic heart diseases to their clinical manifestations and possible complications. Recognize the role of physicians as members of the health care professional team and perform responsibilities in compliance with the professional structure. Relate etiology, epidemiology, pathophysiology, laboratory diagnosis, and clinical features of ischemic heart diseases to understand their pharmacotherapeutic approach.  Overview  Ischemic heart diseases (IHD) encompass several closely related syndromes caused by myocardial ischemia; an imbalance between cardiac blood supply (perfusion) and myocardial oxygen and nutritional requirements.  IHD remains the leading cause of mortality, accounting for 7 million deaths worldwide each year.  In more than 90% of cases, IHD is a consequence of reduced coronary blood flow secondary to obstructive atherosclerotic vascular disease (risk factors!)  Less frequently, IHD can result from: Increased demand (increased heart rate or hypertension) Diminished blood volume (with hypotension or shock) Diminished oxygenation (pneumonia or CHF) Diminished oxygen-carrying capacity (anemia or CO poisoning). 4  Angina Pectoris  Angina pectoris is an intermittent chest pain caused by transient, reversible myocardial ischemia.  The pain probably is a consequence of the ischemia-induced release of adenosine, bradykinin, and other molecules that stimulate the autonomic afferents.  Three variants are recognized: Typical or stable angina Prinzmetal or variant angina Unstable angina 5  Angina Pectoris  Typical or stable angina: Episodic chest pain associated with particular levels of exertion or some other increased demand (e.g., tachycardia). The pain is classically described as a crushing or squeezing substernal sensation, that can http://www.doctortipster.com/3134-myocardial-infarction radiate down the left arm or to the left jaw. The pain usually is relieved by rest (reducing demand) or by drugs such as nitroglycerin, a vasodilator that decreases the venous blood return to the heart (pre-load) and increases coronary perfusion. 6 https://www.urmc.rochester.edu/highland/departments-centers/cardiology  Angina Pectoris Prinzmetal or variant angina: Occurs at rest and is caused by coronary artery spasm. Although such spasms typically occur on or near existing atherosclerotic plaques, completely normal vessel can be affected. Prinzmetal angina typically responds promptly to vasodilators such as What is typical for Prinzmetal angina is its spontaneous appearance at rest, during sleep or in the course of nitroglycerin and calcium channel ordinary activities. blockers. Prinzmetal Angina Pectoris By Dr. Benteu Darius+ · July 30, 2014 7  Angina Pectoris  Unstable angina (crescendo angina): Characterized by increasingly frequent pain, precipitated by progressively less exertion or even occurring at rest. Unstable angina is associated with plaque disruption and superimposed thrombosis, distal embolization of the thrombus, and/or vasospasm; it is often the harbinger of MI, caused by complete vascular occlusion. https://webpath.med.utah.edu/CVHTML/CV005.html https://webpath.med.utah.edu/CVHTML/CV008.html https://webpath.med.utah.edu/CVHTML/CV009.html Narrowing of the lumen due to build up Significant narrowing due to severe Recent thrombosis in narrowed of atherosclerotic plaque coronary atherosclerosis coronary artery Severe coronary arterial narrowing can lead to angina, ischemia, and infarction, depending on the severity and chronicity of the occlusion. 8  Myocardial Infarction  Epidemiology: Myocardial infarction (MI), also commonly referred to as “heart attack,” is necrosis of heart muscle resulting from ischemia. The major underlying cause of IHD is atherosclerosis (same risk factors). While MIs can occur at virtually any age, the frequency rises progressively with increasing age and with increasing atherosclerotic risk factors. Approximately 10% of MIs occur before age 40, and 45% occur before age 65. Men are at significantly greater risk than women, although the gap progressively narrows with age. In general, women tend to be remarkably protected against MI during their reproductive years. However, menopause is associated with exacerbation of coronary artery disease and IHD is the most common cause of death in elderly women. 9  Myocardial Infarction Pathogenesis: The vast majority of MIs are caused by acute coronary artery thrombosis following disruption of preexisting atherosclerotic plaque. In 10% of MIs, transmural infarction occurs in the absence of atherosclerosis: such infarcts are mostly attributable to coronary artery vasospasm or to embolization from mural thrombi (e.g., in the setting of atrial fibrillation) Occasionally, necrosis affects the myocardium most distal to the epicardial vessels (subendocardial MI). 10  Myocardial Infarction  Pathogenesis:  Transmural infarctions involve the full thickness of the myocardium and are caused by epicardial vessel occlusion through a combination of chronic atherosclerosis and acute thrombosis.  Subendocardial infarctions are limited to the inner third of the myocardium; the most vulnerable region to hypoperfusion and hypoxia. They occur in the setting of transient decreases in oxygen delivery (hypotension, anemia, or pneumonia) or increases in oxygen demand (tachycardia or hypertension), or diffused atherosclerosis. They can also occur when an occlusive thrombus lyses before a full-thickness infarction can develop.  Microscopic infarcts occur in the setting of small vessel occlusions and may not show any diagnostic ECG changes. These can occur in the setting of vasculitis, embolization of mural thrombi, or vessel spasm due to elevated catecholamines, either endogenous (pheochromocytoma or extreme stress), or exogenous (cocaine). 11  Subendocardial Transmural Progression of myocardial necrosis after coronary artery occlusion  Necrosis begins in the subendocardial region and with time expands to involve the entire wall thickness.  A very narrow zone of myocardium immediately beneath the endocardium is spared from necrosis because it can be oxygenated by diffusion from the ventricle. 12  Myocardial Infarction Clinical Features: The classic MI is heralded by severe, crushing substernal chest pain (or pressure) that can radiate to the neck, jaw, epigastrium, or left arm. In contrast to angina pectoris, the http://www.tipdisease.com/2013/09/causes-mechanism-symptoms-of-heart.html associated pain typically lasts several minutes to hours, and is not relieved by nitroglycerin or rest. In 10% to 15% of cases, MIs have atypical signs and symptoms and may even be entirely asymptomatic. Such “silent” infarcts are particularly common in patients with underlying diabetes mellitus and in http://www.doctortipster.com/3134-myocardial-infarction elderly persons. 13  Myocardial Infarction Clinical Features:  The pulse generally is rapid and weak, hypotension  Patients are often diaphoretic and nauseous (particularly with posterior wall MIs).  Weakness, light-headedness, vomiting and palpitations…  Dyspnea is common (resultant acute pulmonary congestion and edema).  Cardiogenic shock develops with massive MIs (involving more than 40% of the left ventricle). 14  Myocardial Infarction Electrocardiographic Abnormalities: ST segment elevation Inverted T wave Deep Q wave  Arrhythmias caused by electrical abnormalities in ischemic myocardium and conduction system are common.  Sudden cardiac death from a lethal arrhythmia accounts for the vast majority of MI-related deaths occurring before hospitalization. 15  Myocardial Infarction  Laboratory Evaluation:  CK-MB activity begins to rise within 2 to 4 hours of MI, peaks at 24 to 48 hours, and returns to normal within approximately 72 hours.  An absence of a change CK and CK-MB levels during the first 2 days after the chest pain essentially excludes the diagnosis of MI.  Troponins TnI and TnT normally are not found in the circulation; however, after acute MI, both are detectable within 2 to 4 hours, with levels peaking at 24 to 48 hours and remaining elevated for 7 to 10 days.  Persistence of elevated troponin levels for Troponins and CK-MB have high approximately 10 days allows the diagnosis specificity and sensitivity for of an acute MI long after CK-MB levels have myocardial damage. returned to normal. Acute Myocardial Infarction H. Michael Bolooki 16 Arman Askari  Myocardial Infarction Consequences and Complications:  Contractile dysfunction: In most cases, there is some degree of left ventricular failure manifested as hypotension, pulmonary congestion, and pulmonary edema. Cardiogenic shock occurs in roughly 10% of patients with transmural MIs and typically is associated with infarcts that damage 40% or more of the left ventricle.  Right ventricular infarction (1% to 3%): Right sided heart failure is a common outcome, leading to venous circulation pooling and systemic hypotension.  Papillary muscle dysfunction: Dysfunctional papillary muscles can be poorly contractile as a result of ischemia, leading to postinfarct mitral regurgitation. Much later, papillary muscle fibrosis and shortening or global ventricular dilation also can cause mitral valve insufficiency. 17  Myocardial Infarction Consequences and Complications:  Myocardial rupture (1% to 5%), within 3 to 7 days after infarction  Left ventricular wall rupture is most common, usually resulting in rapidly fatal hemopericardium and cardiac tamponade (transmural). Ventricular septal rupture creates a VSD with left-to-right shunting. Papillary muscle rupture leads to severe mitral regurgitation.  Arrhythmias (90%): A third of persons with ST elevation MIs (STEMIs) will die, usually of an arrhythmia within an hour of symptom onset, before they receive appropriate medical attention. The risk of serious arrhythmias (e.g., ventricular fibrillation) is greatest in the first hour and declines thereafter. 18  Myocardial Infarction Consequences and Complications: Anterior wall myocardial rupture Ventricular septal rupture Papillary muscle rupture 19  Myocardial Infarction Consequences and Complications:  Mural thrombus: The combination of attenuated myocardial contractility (causing stasis) and endocardial damage (causing a thrombogenic surface) can foster mural thrombosis eventually leading to thromboembolism.  Pericarditis: (2 to 3 days post-MI) This is an epicardial manifestation of the underlying myocardial inflammation (Transmural MI)  Ventricular aneurysm: (late complication) Most commonly results from a large transmural infarct that heals with the formation of a thinned wall of scar tissue. Frequently give rise to formation of mural thrombi, arrhythmias, and heart failure, they do not rupture. 20  Myocardial Infarction Consequences and Complications: Fibrinous pericarditis Mural thrombus with a hemorrhagic surface Large apical left ventricular aneurysm With subendocardial infarcts, thrombi may form on the endocardial surface, but pericarditis, rupture, and aneurysms rarely occur. 21  References Robbins Basic Pathology, 10th edition, by Vinay Kumar, Abul K. Abbas and Jon C. Aster. Elsevier, ISBN: 9780323353175, 2018 ROBBINS Basic Pathology 9th Edition Source of the cover image: http://www.nattokinase.org/blog/angina 22 Thank you… 23