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  Outlin I. Overview e II. Angina Pectoris  Typical or stable angina  Prinzmetal or variant angina II Myocardial Infarcti...

Pathophysiology PHMU 534 Lecture 7 Ischemic Heart Diseases Prof. Dr. Nabila Hamdi MD, PhD in Molecular Medicine and Pathology  Outlin I. Overview e II. Angina Pectoris  Typical or stable angina  Prinzmetal or variant angina II Myocardial Infarction  Unstable angina I.  Epidemiology  Pathogenesis  Clinical Features  Electrocardiographic Abnormalities  Laboratory Evaluation  Clinical Consequences & Complications 2  Competenc ies 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.  Overvi ew  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  Angina Pectoris 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  Typical or stable Pectoris angina: Episodic chest pain associated with particular levels of exertion or some other increased demand (e.g., tachycardia). http://www.doctortipster.com/3134-myocardial-i nfarction The pain is classically described as a crushing or squeezing substernal sensation, that can 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 6 coronary perfusion. https:// www.urmc.rochester.edu/highland/departments-centers/cardio  Angina Pectoris  Prinzmetal or variant angina: Occurs at restand is causedby coronary artery spasm. Although such spasms typically occur on or near existing atherosclerotic plaques, completely normal vessel can be affected. promptlyto vasodilators What is typical for Prinzmetal angina is its spontaneous appearance at rest, during such nitroglycerin as and Prinzmetal angina typically sleep or in the course of ordinary activities. calcium channel Prinzmetal Angina Pectoris responds By Dr. Benteu Darius+ · July 30, 2014 blockers. 7  Angina  UnstablePectoris 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/ https://webpath.med.utah.edu/CVHTML/ https://webpath.med.utah.edu/CVHTML/ CV005.html CV008.html CV009.html Narrowing of the lumen due to Significant narrowing due to Recent thrombosis in build up of severe coronary narrowed coronary atherosclerotic plaque atherosclerosis artery Severe coronary arterial narrowing can lead to angina, ischemia, and infarction, depending on the severity 8 and chronicity of the occlusion.  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  Myocardial Infarction  Pathogenesis: The vast majority of MIs are caused by acute artery thrombosis coronar y of preexisting following disrupti atherosclerotic on 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 1 MI). 0  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 1 1  Subendocardi al Transmur al Progression of myocardial necrosis after coronary artery occlusion  Necrosis begins in the subendocardial region and with time expands to involve the entire wall thickness. 1  A very narrow zone of myocardium immediately beneath the endocardium is 2  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 angina http://www.tipdisease.com/2013/09/causes-mechanism-symptoms- of-heart.html associated to pectoris, the minutes to hours, and is not typically relieved pain by lasts several nitroglycerin or rest. Atypical Infarcts: In 10% to 15% of cases, MIs have atypical signs and symptoms infarcts and are may even becommon particularly entirelyin patients asymptomatic. with Such underlying http://www.doctortipster.com/3134-myocardial-i “silent”diabetes mellitus and in nfarction elderly persons. 1 3  Myocardial Infarction  Clinical Features:  The pulse generally is rapid and weak,  hypotension Patients are often diaphoretic and nauseouswit (particularly h posterior wall MIs).  Weakness, light-headedness, vomiting and palpitations…   Dyspnea Cardiogenic is common shock develops (resultant with massive MIsacute pulmonary congestion (involving more andleft ventricle). than 40% of the edema). 1 4  Myocardial Infarction  Electrocardiographic Abnormalities: ST segment elevation Inverted T Deep Q  Arrhythmias caused wave wavein ischemic myocardium and by electrical abnormalities conduction system are common.  Sudden cardiac death from a lethal arrhythmia accounts for the vast majority of MI-related deaths occurring before hospitalization. 1 5  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  Persistence levels peakingofat elevated troponin 24 to 48 hours and Troponins and CK-MB levels for approximately 10 remaining elevated for 7 to 10 days have high specificity allows days. the diagnosis of an acute MI and sensitivity for long after CK-MB levels have myocardial damage. returned to normal. Acute Myocardial Infarction 1 H. Michael Bolooki Arman 6  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  Myocardial Infarctionand Consequences 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,  Myocardial Infarction  Consequences and Complications: Anterior wall Ventricular septal Papillary muscle myocardial rupture rupture rupture 1 9  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 failure, thedo not they 2 formation rupture. of a thinned wall of scar tissue. 0  Myocardial Infarction and  Consequences Complications: Fibrinous Mural pericarditis Large apical left ventricular thrombus with a hemorrhagic aneurysm surface With subendocardial infarcts, thrombi may form on the endocardial surface, but pericarditis, rupture, and aneurysms rarely occur. 2 1  Referenc es 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 2 2 Thank you… 2 3