Myocardial Infarction[Heart Attack]; Causes, Pathogenesis, Signs & Symptoms, Diagnosis & Treatment

normal cardiac function is strictly dependent upon the continuous flow of blood through the coronary arteries because myocytes generate energy almost exclusively through mitochondrial oxidative physician ischemic heart disease or ihd is a broad term that includes several closely related syndromes caused by myocardial ischemia and it is the leading cause of mortality around the world accounting for approximately 7 million deaths each year the clinical presentation of ischemic heart disease may include one or more of the following cardiac syndromes angina pectoris which could be either stable angina or unstable angina acute myocardial infarction sudden cardiac death and chronic ischemic heart disease with congestive heart failure the term acute coronary syndrome is applied to any of the three catastrophic manifestations of ischemic heart disease unstable angina acute myocardial infarction and sudden cardiac death in more than 90 percent of cases the cause of ischemic heart disease is reduced coronary blood flow due to atherosclerotic obstruction some uncommon causes of ischemic heart disease include increased demand of the heart such as in cardiac hypertrophy diminished blood flow due to shock diminished oxygenation in conditions like pneumonia and congestive heart failure and diminished oxygen carrying capacity such as in anemia and carbon monoxide poisoning now let's come to our original topic myocardial infarction or heart attack in general is death of the cardiac muscle due to severe prolonged ischemia major underlying cause of myocardial infarction is coronary artery atherosclerosis myocardial infarctions can occur at any age but the frequency rises with increasing age and with increasing atherosclerosis risk factors generally men are at a higher risk than women and women in reproductive age are less affected because of their normal estrogen production however after menopause the risk increases now let's discuss about the pathophysiology of myocardial infarction as mentioned earlier the commonest cause for myocardial infarction is coronary artery atherosclerosis the ultimate edo logic factor that leads to atherosclerosis induced myocardial infarction is changes in the atherosclerotic plaques which is referred to as the acute plaque change i have created a separate video on the pathology of atherosclerosis if you want to learn more details on these acute changes you can watch that video as well i will put a link in the description acute plaque change gives rise to one or more of the following manifestations rupture or fissuring of the atherosclerotic plaque or erosion or ulceration of the plaque both of which give rise to superimposed thrombosis or bleeding into the plaque which may result in expansion of the plaque as we already know from our physiology knowledge during a thrombogenic episode the affected arteries constrict and the size of the thrombus increases due to the activation of coagulation cascade so ultimately the thrombus expands more and causes complete obstruction of the affected coronary artery in addition to atherosclerosis less common causes of myocardial infarction include the following wasospasm of coronary arteries emboli from the left atrium typically associated with atrial fibrillation cardiac mural thrombi and infective endocarditis coronary artery vasculitis hematologic abnormalities like sickle cell disease and amyloid deposition of the vascular walls whatever the underlying etiology coronary arterial obstruction diminishes blood flow to a region of the myocardium leading to ischemia and rapid myocardial dysfunction with prolonged vascular compromise myocyte death will occur the anatomic region supplied by that artery is referred to as the area at risk the outcome of coronary artery obstruction predominantly depends on the severity and the duration of flow obstruction with inadequate oxygen supply aerobic metabolism ceases within minutes leading to inadequate production of high-energy phosphates such as creatine phosphate and atp which are essentially required for myocardial contraction and accumulation of noxious metabolites such as lactic acid as a consequence of increased anaerobic metabolism as myocardial function strictly depends upon continuous oxygen and nutrient supply myocardial contraction ceases within a minute or so of the onset of severe ischemia therefore it is important to note that reduced contractility of the myocardium can lead to heart failure long before the myocyte death and most importantly the earliest manifestations of myocyte ischemia like cellular swelling glycogen depletion and myofibrillar relaxation are potentially reversible therefore only the severe ischemia lasting for 20 to 30 minutes or longer leads to irreversible damage of cardiac myocytes myocyte death will lead to disruption of their membrane integrity which results in leakage of intracellular macromolecules into the myocardial interstitial tissue and then into the microvisculature this forms the basis for blood tests that can detect irreversible myocyte damage early we will discuss about these tests later in this video following irreversible myocyte damage injury to the microvisculature ensues we know that heart wall consists of three main layers endocardium which is the inner layer consisting of squamous epithelial cells myocardium which is the middle layer consisting of cardiac muscle and the pericardium which is the outermost layer consisting of several layers if we take the myocardium alone it can be divided into three parts to explain different types of myocardial infarction inner one-third of the myocardium is called the sub-endocardium the middle one-third is called the mid-myocardium and the outermost one-third of the myocardium is called sub-epicardium here is a crude diagram of the blood supply of heart muscle coronary arteries give rise to small epicardial arteries which are located within the epicardial layer of the pericardium these epicardial arteries then give rise to small intramural arteries that penetrate the heart muscle in order to supply the cardiac myocytes different types of intramural arteries join at the sub-endocardium to form sub-endocardial plexus which supplies the inner one-third of the heart muscle because sub-endocardium is the most distal part for the blood to reach it is the least perfused area of the myocardium because of this it is more susceptible to undergo infarction therefore infarction first starts in the sub-endocardial region which is known as sub-endocardial infarction if the occlusion persists the infarction becomes transmural with time extending over the whole thickness of the heart muscle precise location size and specific morphologic features of an acute myocardial infarction depends on the following factors the location severity and rate of development of coronary occlusion the size of the vascular bed supplied by the obstructed vessels the duration of occlusion metabolic and oxygen demand of the myocardium at risk the extent of collateral blood vessels the presence site and severity of coronary artery spasm and other factors like heart rate cardiac rhythm and blood oxygenation now let's discuss a bit about the different types of infarction first let's take sub-endocardial infarction as already mentioned sub-endocardium is the least perfused area of the myocardium therefore it is more vulnerable to undergo infarction sub-endocardial infarction typically involves the inner one-third of the myocardium endocardium is usually spared in sub-endocardial infarctions because oxygen and nutrients are diffused directly from the blood inside heart chambers infarction limits to the sub-endocardium due to the early lysis of clots either spontaneously or therapeutically before the infarction becomes transmural if the occlusion persists the infarction becomes transmural with time they can also occur with prolonged severe reductions in systemic blood pressure such as in shock in contrast to atherosclerosis-induced sub-endocardial infarctions sub-endocardial infarctions result from global hypotension are typically circumferential ecg changes in sub-endocardial infarctions are characterized by st segment depression st depression is reversible if the ischemia is only transient but persists if ischemia is severe enough to produce an infarction and sometimes a t-wave inversion can be seen with or without st depression sub-endocardial infarctions are typically referred to as non-st segment elevation myocardial infarctions because as you will see later transmural infarctions are associated with st segment elevation on an ecg transmural infarction involves the full thickness of the myocardium and also the endocardium transmiral infarctions are associated with a combination of chronic coronary atherosclerosis acute plaque change and superimposed thrombosis it is important to note that transmural infarctions almost always occur in the left ventricle and sometimes the ventricular septum is also involved and they are extremely rare in the right ventricles and atria this diagram shows the sequence of ecg changes during a transmural infarction one of the earliest changes is st segment elevation as highlighted by the yellow square after that a q wave develops with inversion of the t wave with time st elevation disappears with normalization of the t wave however the q wave persists and it indicates established transmural infarction or healed previous infarctions thrombolytic therapy is aimed at lysing the clot as early as possible to limit the size of the infert therefore thrombolytic agents are given in the presence of st elevation before development of q waves transmiral infarctions are typically referred to as st segment elevation myocardial infarctions or steamy there is another type of infarction called multifocal micro infarctions these infarctions typically occur when there is obstruction in smaller intramural vessels there are small multiple infected areas in the myocardium most common causes of these infections are micro embolization vasculitis and vascular spasm as you already know from your anatomy knowledge there are three main coronary arteries right coronary artery and the two branches of the left coronary artery left anterior descending and circumflex artery left anterior descending artery is the commonly involved one accounting for about 40 to 50 percent of cases area of the infarct involves the anterior wall of the left ventricle near the apex anterior portion of the ventricular septum and the apex circumferentially right coronary artery is involved in 30 to 40 percent of myocardial infarction cases area of the infarct involves the inferior or posterior wall of the left ventricle posterior portion of the ventricular septum and in rare cases posterior free wall of the right ventricle involvement of the left circumflex artery is less common and accounts for about 15 to 20 percent of cases the area of infarction involves the lateral wall of the left ventricle except at the apex now let's discuss about the morphologic features of myocardial infarction gross and microscopic appearance of an infertile depends on the duration of survival of the patient following the infarction areas of damage undergo a progressive sequence of morphologic changes involving typical ischemic coagulative necrosis followed by inflammation and repair first let's see what are the gross features of myocardial infarction infarctions less than 12 hours old are usually not apparent on gross examination if the inference lead to death of the person by two to three hours following the infarction necrotic area can be identified by immersion of tissue slices in a solution of triphenyl tetrazolium chloride this gross histochemical stain imparts a brick red color to the intact non-infected viable myocardial tissue due to the presence of lactate dehydrogenase enzyme but the necrotic myocytes lack this enzyme due to its leakage through their damaged cell membranes therefore the necrotic area appears pale with this stain as indicated by the large arrow in the picture more whitish area denoted by the small arrowhead indicates a well-heeled previous infarction by 12 to 24 hours after the infrated area becomes reddish blue in color due to stagnated trapped blood thereafter the infarct becomes progressively more sharply defined soft and yellow tan in color by 10 days to two weeks the area is surrounded by hyperemia and highly vascularized granulation tissue over the next few weeks the injured region becomes a fibrous scar in histopathology typical changes of coagulative necrosis become detectable in the first six to twelve hours wavy myocardial fibers may present at the periphery of the infert these changes probably result from the forceful systolic pulling of the viable fibers on non-contractile dead fibers causing stretching and folding contraction bands may also present these are denoted by the black arrows in this picture necrotic muscle elicits acute inflammation which is more prominent in first three days macrophages remove necrotic myocytes which occurs within three to seven days following the infarction over time damaged tissue is progressively replaced by highly vascularized granulation tissue and ultimately the infertile is replaced by a fibrous scar now let's discuss about the clinical features of myocardial infarction patients with myocardial infarction classically present with prolonged chest pain which typically lasts for more than 30 minutes chest pain is usually substernal and often radiates up to the neck shoulder jaw and down the left arm and it is felt like crushing stabbing or squeezing on the chest the patient is tachycardic with irregular pulse the respiratory rate is increased due to pulmonary congestion and anxiety patients may experience profuse sweating nausea and vomiting and dyspnea laboratory evaluation of myocardial infarction is based on measuring the blood levels of proteins that leak out of irreversibly damaged myocytes most useful markers are cardiac specific troponins troponin t and troponin i and the mb fraction of creatine kinase cardiac troponins are proteins that regulate the calcium-mediated contraction of the myocytes and they are the most sensitive and specific biomarkers of myocardial infarction they are normally not detectable in the circulation and the levels begin to rise within 3 to 12 hours following an infarction troponin eye returns to normal levels in 5 to 10 days following the infarction whereas troponin t takes about 5 to 14 days creatine kindness is an enzyme expressed in brain myocardium and skeletal muscle it is a dimer composed of two isoforms m and b ckm is found in both cardiac and skeletal muscles ckbb is predominant in brain and lungs and ckmb is principally present in the cardiac muscle but skeletal muscle also contains a lesser amount therefore ckmb is a sensitive marker but not specific levels begin to rise within three to 12 hours after an infarction and peaks at about 24 hours unlike troponins ckm beer returns to normal levels fairly quickly approximately within 48 to 72 hours now let's discuss about possible interventions that can be made to reduce the size of the infertile these are typically made when the patient presence during or immediately after a myocardial infarction and they are aimed at infertile modification by reperfusion which restores the blood flow to the ischemic myocardium these interventions include the following thrombolysis angioplasty stent placement and coronary artery bypass grafting surgery the main goal of these interventions is to dissolve mechanically alter or bypass the lesion that caused the acute infarction typical therapeutics that are given in the hospital include the following morphine to relieve pain and improve dyspnea symptoms anti-platelet agents such as aspirin p2y12 receptor inhibitors and glycoprotein 2b 3a inhibitors anticoagulant therapy with heparin direct thrombin inhibitors and factor 10 inhibitors to prevent clot propagation nitrates to induce waso dilation and reverse wasospasm beta blockers to decrease myocardial oxygen demand and to reduce the risk of arrhythmias antiarrhythmics to manage arrhythmias ace inhibitors to limit ventricular dilation and oxygen supplementation to improve blood oxygen saturation finally let's discuss about the complications of myocardial infarction some of the early complications include the following contractal dysfunction myocardial infarctions produce abnormalities in the left ventricular function roughly proportionate to the size of the infert there is some degree of left ventricular failure with hypotension pulmonary congestion and pulmonary edema severe pump failure also known as cardiogenic shock develops in 10 to 15 percent of patients typically with large inference cardiogenic shock has approximately 70 percent of mortality rate right ventricular inverts give rise to right-sided heart failure with resultant pooling of blood in the venous circulation followed by systemic hypotension another major complication is arrhythmias which is the major cause for sudden death following an acute myocardial infarction common myocardial infarction-associated arrhythmias are sinus bradycardia atrial fibrillation heart block ventricular tachycardia ventricular fibrillation and ventricular premature contractions progression of the infarction occurs in persistent coronary artery obstruction at first there will be a sub-endocardial infarction followed by transmural infarction and expansion of the infarction to the viable myocardium formation of mural thrombi is another complication commonly occurs with transmural infarctions due to the endocardial damage the highly thrombogenic sub endocardium is exposed and due to the reduced contractility of the myocardium stasis of blood will occur both of these factors contribute to formation of cardiac mural thrombi mural thrombi are the most common cause of systemic thromboembolism common sites of embolization include splenic renal and cerebral arteries and lower extremities myocardial rupture is another complication typically occurs with transmural infarctions rupture of the free ventricular wall which is the more common mechanism gives rise to hemopericardium and cardiac tamponade rupture of the ventricular septum which is less common gives rise to acute vsd and left to right shunting rupture of the papillary muscle the least common one gives rise to acute onset of severe mitral regurgitation ventricular rupture occurs less frequently in patients with prior myocardial infarctions because associated fibrotic scarring tends to inhibit myocardial tearing pericarditis is another complication which gives rise to pericardial effusions other indirect complications are deep vein thrombosis and pulmonary embolism late complications of myocardial infarction include the following formation of cardiac aneurysms following a myocardial infarction the necrotic area ultimately heals by fibrosis this causes weakness of the ventricular wall and it bulges out due to the pressure within the ventricle which causes formation of aneurysms moreover stasis of blood within the aneurysm leads to thrombosis and thromboembolism aneurysms also cause reduced cardiac output which manifests as congestive heart failure dressler's syndrome is another late complication it is an autoimmune condition which occurs in response to cardiac elements released during infarction commonly manifests as pericarditis my trowel incompetence may occur due to papillary muscle fibrosis caused by ischemia and healed infarctions congestive heart failure is another direct long-term complication either due to acute myocardial infarction or chronic ischemic heart disease chronic ischemic heart disease causes diffuse fibrosis of the myocardium whereas acute myocardial infarction causes localized fibrosis both of which lead to reduced myocardial contratility and congestive heart failure okay that is all i wish to discuss in this video hope you found this video helpful if you have any question or doubt regarding this topic feel free to post them in the comment section thanks for watching see you soon in the next video